메뉴 건너뛰기




Volumn 24, Issue 7, 2015, Pages 1057-1074

Marginally hydrophobic transmembrane α-helices shaping membrane protein folding

Author keywords

aquaporin 1; hydrophobicity; marginally hydrophobic transmembrane helices; membrane protein folding

Indexed keywords

AMINO ACID; AQUAPORIN 1; HYDROCARBON; LIPID; MEMBRANE LIPID; MEMBRANE PROTEIN; SEC61ALPHA TRANSLOCON; SEC61BETA TRANSLOCON; SEC61GAMMA TRANSLOCON; SIGNAL RECOGNITION PARTICLE; TRANSLOCON; UNCLASSIFIED DRUG;

EID: 84946032322     PISSN: 09618368     EISSN: 1469896X     Source Type: Journal    
DOI: 10.1002/pro.2698     Document Type: Review
Times cited : (31)

References (180)
  • 1
  • 4
    • 85047924580 scopus 로고    scopus 로고
    • Israelachvili J.N. editor. 3rd ed. Boston: Academic Press
    • Israelachvili JN, editor (2011). Intermolecular and surface forces, 3rd ed. Boston: Academic Press.
    • (2011) Intermolecular and Surface Forces
  • 6
    • 84906884220 scopus 로고    scopus 로고
    • Life at the border: Adaptation of proteins to anisotropic membrane environment
    • Pogozheva ID, Mosberg HI, Lomize AL, (2014). Life at the border: adaptation of proteins to anisotropic membrane environment. Protein Sci 23: 1165-1196.
    • (2014) Protein Sci , vol.23 , pp. 1165-1196
    • Pogozheva, I.D.1    Mosberg, H.I.2    Lomize, A.L.3
  • 7
    • 66549128460 scopus 로고    scopus 로고
    • The role of lipid composition for insertion and stabilization of amino acids in membranes
    • Johansson AC, Lindahl E, (2009). The role of lipid composition for insertion and stabilization of amino acids in membranes. J Chem Phys 130.
    • (2009) J Chem Phys , vol.130
    • Johansson, A.C.1    Lindahl, E.2
  • 8
    • 84895532708 scopus 로고    scopus 로고
    • Cardiolipin-dependent formation of mitochondrial respiratory supercomplexes
    • Mileykovskaya E, Dowhan W, (2014). Cardiolipin-dependent formation of mitochondrial respiratory supercomplexes. Chem Phys Lipids 179: 42-48.
    • (2014) Chem Phys Lipids , vol.179 , pp. 42-48
    • Mileykovskaya, E.1    Dowhan, W.2
  • 9
    • 84878723802 scopus 로고    scopus 로고
    • In vitro reconstitution of lipid-dependent dual topology and postassembly topological switching of a membrane protein
    • Vitrac H, Bogdanov M, Dowhan W, (2013). In vitro reconstitution of lipid-dependent dual topology and postassembly topological switching of a membrane protein. Proc Natl Acad Sci USA 110: 9338-9343.
    • (2013) Proc Natl Acad Sci USA , vol.110 , pp. 9338-9343
    • Vitrac, H.1    Bogdanov, M.2    Dowhan, W.3
  • 11
    • 84964312418 scopus 로고    scopus 로고
    • Phospholipase d signaling pathways and phosphatidic acid as therapeutic targets in cancer
    • Bruntz RC, Lindsley CW, Brown HA, (2014). Phospholipase d signaling pathways and phosphatidic acid as therapeutic targets in cancer. Pharmacol Rev 66: 1033-1079.
    • (2014) Pharmacol Rev , vol.66 , pp. 1033-1079
    • Bruntz, R.C.1    Lindsley, C.W.2    Brown, H.A.3
  • 14
    • 7044264920 scopus 로고    scopus 로고
    • Diversity and versatility of lipid-protein interactions revealed by molecular genetic approaches
    • Dowhan W, Mileykovskaya E, Bogdanov M, (2004). Diversity and versatility of lipid-protein interactions revealed by molecular genetic approaches. Biochim Biophys Acta 1666: 19-39.
    • (2004) Biochim Biophys Acta , vol.1666 , pp. 19-39
    • Dowhan, W.1    Mileykovskaya, E.2    Bogdanov, M.3
  • 15
    • 0022080948 scopus 로고
    • Intrinsic curvature hypothesis for biomembrane lipid composition: A role for nonbilayer lipids
    • Gruner SM, (1985). Intrinsic curvature hypothesis for biomembrane lipid composition: a role for nonbilayer lipids. Proc Natl Acad Sci USA 82: 3665-3669.
    • (1985) Proc Natl Acad Sci USA , vol.82 , pp. 3665-3669
    • Gruner, S.M.1
  • 16
    • 84878131033 scopus 로고    scopus 로고
    • Checks and balances in membrane phospholipid class and acyl chain homeostasis, the yeast perspective
    • de Kroon AIPM, Rijken PJ, De Smet CH, (2013). Checks and balances in membrane phospholipid class and acyl chain homeostasis, the yeast perspective. Prog Lipid Res 52: 374-394.
    • (2013) Prog Lipid Res , vol.52 , pp. 374-394
    • De Kroon, A.1    Rijken, P.J.2    De Smet, C.H.3
  • 17
    • 79957470462 scopus 로고    scopus 로고
    • Lipid-protein interactions
    • Lee AG, (2011). Lipid-protein interactions. Biochem Soc Trans 39: 761-766.
    • (2011) Biochem Soc Trans , vol.39 , pp. 761-766
    • Lee, A.G.1
  • 18
    • 67650732710 scopus 로고    scopus 로고
    • Lipid-dependent membrane protein topogenesis
    • Dowhan W, Bogdanov M, (2009). Lipid-dependent membrane protein topogenesis. Annu Rev Biochem 78: 515-540.
    • (2009) Annu Rev Biochem , vol.78 , pp. 515-540
    • Dowhan, W.1    Bogdanov, M.2
  • 19
    • 7044224838 scopus 로고    scopus 로고
    • Membrane fluidity and its roles in the perception of environmental signals
    • Los DA, Murata N, (2004). Membrane fluidity and its roles in the perception of environmental signals. Biochim Biophys Acta 1666: 142-157.
    • (2004) Biochim Biophys Acta , vol.1666 , pp. 142-157
    • Los, D.A.1    Murata, N.2
  • 20
    • 0026729232 scopus 로고
    • Structure of a fluid dioleoylphosphatidylcholine bilayer determined by joint refinement of X-ray and neutron diffraction data. III. Complete structure
    • Wiener MC, White SH, (1992). Structure of a fluid dioleoylphosphatidylcholine bilayer determined by joint refinement of X-ray and neutron diffraction data. III. Complete structure. Biophys J 61: 434-447.
    • (1992) Biophys J , vol.61 , pp. 434-447
    • Wiener, M.C.1    White, S.H.2
  • 22
    • 0027179487 scopus 로고
    • Phospholipids in animal eukaryotic membranes: Transverse asymmetry and movement
    • Zachowski A, (1993). Phospholipids in animal eukaryotic membranes: transverse asymmetry and movement. Biochem J 294: 1-14.
    • (1993) Biochem J , vol.294 , pp. 1-14
    • Zachowski, A.1
  • 23
    • 84898993452 scopus 로고    scopus 로고
    • The basic structure and dynamics of cell membranes: An update of the Singer-Nicolson model
    • Goni FM, (2014). The basic structure and dynamics of cell membranes: an update of the Singer-Nicolson model. Biochim Biophys Acta 1838: 1467-1476.
    • (2014) Biochim Biophys Acta , vol.1838 , pp. 1467-1476
    • Goni, F.M.1
  • 24
    • 70349469585 scopus 로고    scopus 로고
    • Domains in biological membranes
    • Lindner R, Naim HY, (2009). Domains in biological membranes. Exp Cell Res 315: 2871-2878.
    • (2009) Exp Cell Res , vol.315 , pp. 2871-2878
    • Lindner, R.1    Naim, H.Y.2
  • 26
    • 0015514472 scopus 로고
    • The fluid mosaic model of the structure of cell membranes
    • Singer SJ, Nicolson GL, (1972). The fluid mosaic model of the structure of cell membranes. Science 175: 720-731.
    • (1972) Science , vol.175 , pp. 720-731
    • Singer, S.J.1    Nicolson, G.L.2
  • 27
    • 0031740283 scopus 로고    scopus 로고
    • How lipids interact with an intrinsic membrane protein: The case of the calcium pump
    • Lee AG, (1998). How lipids interact with an intrinsic membrane protein: the case of the calcium pump. Biochim Biophys Acta 1376: 381-390.
    • (1998) Biochim Biophys Acta , vol.1376 , pp. 381-390
    • Lee, A.G.1
  • 28
    • 0015473745 scopus 로고
    • Membrane proteins
    • Guidotti G, (1972) Membrane proteins. Annu Rev Biochem 41: 731-752.
    • (1972) Annu Rev Biochem , vol.41 , pp. 731-752
    • Guidotti, G.1
  • 29
    • 33845424528 scopus 로고    scopus 로고
    • Amino-acid solvation structure in transmembrane helices from molecular dynamics simulations
    • Johansson AC, Lindahl E, (2006). Amino-acid solvation structure in transmembrane helices from molecular dynamics simulations. Biophys J 91: 4450-4463.
    • (2006) Biophys J , vol.91 , pp. 4450-4463
    • Johansson, A.C.1    Lindahl, E.2
  • 30
    • 77954299061 scopus 로고    scopus 로고
    • A comprehensive comparison of transmembrane domains reveals organelle-specific properties
    • Sharpe HJ, Stevens TJ, Munro S, (2010). A comprehensive comparison of transmembrane domains reveals organelle-specific properties. Cell 142: 158-169.
    • (2010) Cell , vol.142 , pp. 158-169
    • Sharpe, H.J.1    Stevens, T.J.2    Munro, S.3
  • 31
    • 0038364008 scopus 로고    scopus 로고
    • Lipid-protein interactions in biological membranes: A structural perspective
    • Lee AG, (2003) Lipid-protein interactions in biological membranes: a structural perspective. Biochim Biophys Acta 1612: 1-40.
    • (2003) Biochim Biophys Acta , vol.1612 , pp. 1-40
    • Lee, A.G.1
  • 32
    • 0032509102 scopus 로고    scopus 로고
    • Proline-induced disruption of a transmembrane alpha-helix in its natural environment
    • Nilsson I, Saaf A, Whitley P, Gafvelin G, Waller C, von Heijne G, (1998). Proline-induced disruption of a transmembrane alpha-helix in its natural environment. J Mol Biol 284: 1165-1175.
    • (1998) J Mol Biol , vol.284 , pp. 1165-1175
    • Nilsson, I.1    Saaf, A.2    Whitley, P.3    Gafvelin, G.4    Waller, C.5    Von Heijne, G.6
  • 33
    • 0031740415 scopus 로고    scopus 로고
    • Hydrophobic mismatch between proteins and lipids in membranes
    • Killian JA, (1998). Hydrophobic mismatch between proteins and lipids in membranes. Biochim Biophys Acta 1376: 401-415.
    • (1998) Biochim Biophys Acta , vol.1376 , pp. 401-415
    • Killian, J.A.1
  • 34
    • 7244244196 scopus 로고    scopus 로고
    • Lipids do influence protein function-the hydrophobic matching hypothesis revisited
    • Jensen M, Mouritsen OG, (2004). Lipids do influence protein function-the hydrophobic matching hypothesis revisited. Biochim Biophys Acta 1666: 205-226.
    • (2004) Biochim Biophys Acta , vol.1666 , pp. 205-226
    • Jensen, M.1    Mouritsen, O.G.2
  • 35
    • 0032581038 scopus 로고    scopus 로고
    • Influence of lipid/peptide hydrophobic mismatch on the thickness of diacylphosphatidylcholine bilayers. A 2H NMR and ESR study using designed transmembrane alpha-helical peptides and gramicidin a
    • de Planque MR, Greathouse DV, Koeppe RE, Schafer H, Marsh D, Killian JA, (1998). Influence of lipid/peptide hydrophobic mismatch on the thickness of diacylphosphatidylcholine bilayers. A 2H NMR and ESR study using designed transmembrane alpha-helical peptides and gramicidin a. Biochemistry 37: 9333-9345.
    • (1998) Biochemistry , vol.37 , pp. 9333-9345
    • De Planque, M.R.1    Greathouse, D.V.2    Koeppe, R.E.3    Schafer, H.4    Marsh, D.5    Killian, J.A.6
  • 36
    • 1642570286 scopus 로고    scopus 로고
    • Modulation of the bilayer thickness of exocytic pathway membranes by membrane proteins rather than cholesterol
    • Mitra K, Ubarretxena-Belandia I, Taguchi T, Warren G, Engelman DM, (2004) Modulation of the bilayer thickness of exocytic pathway membranes by membrane proteins rather than cholesterol. Proc. Natl. Acad. Sci. U.S.A. 101: 4083-4088.
    • (2004) Proc. Natl. Acad. Sci. U.S.A , vol.101 , pp. 4083-4088
    • Mitra, K.1    Ubarretxena-Belandia, I.2    Taguchi, T.3    Warren, G.4    Engelman, D.M.5
  • 38
    • 0035979370 scopus 로고    scopus 로고
    • Modulation of na,K-ATPase and Na-ATPase activity by phospholipids and cholesterol. I. Steady-state kinetics
    • Cornelius F, (2001). Modulation of na,K-ATPase and Na-ATPase activity by phospholipids and cholesterol. I. Steady-state kinetics. Biochemistry 40: 8842-8851.
    • (2001) Biochemistry , vol.40 , pp. 8842-8851
    • Cornelius, F.1
  • 39
    • 0029165107 scopus 로고
    • An investigation of the role of transmembrane domains in golgi protein retention
    • Munro S, (1995). An investigation of the role of transmembrane domains in golgi protein retention. EMBO J 14: 4695-4704.
    • (1995) EMBO J , vol.14 , pp. 4695-4704
    • Munro, S.1
  • 41
    • 48249116482 scopus 로고    scopus 로고
    • Pip2 is a necessary cofactor for ion channel function: How and why?
    • Suh BC, Hille B, (2008). pip2 is a necessary cofactor for ion channel function: how and why? Annu Rev Biophys 37: 175-195.
    • (2008) Annu Rev Biophys , vol.37 , pp. 175-195
    • Suh, B.C.1    Hille, B.2
  • 42
    • 33845313646 scopus 로고    scopus 로고
    • PI(3,4,5)p3 and PI(4,5)p2 lipids target proteins with polybasic clusters to the plasma membrane
    • Heo WD, Inoue T, Park WS, Kim ML, Park BO, Wandless TJ, Meyer T, (2006). PI(3,4,5)p3 and PI(4,5)p2 lipids target proteins with polybasic clusters to the plasma membrane. Science 314: 1458-1461.
    • (2006) Science , vol.314 , pp. 1458-1461
    • Heo, W.D.1    Inoue, T.2    Park, W.S.3    Kim, M.L.4    Park, B.O.5    Wandless, T.J.6    Meyer, T.7
  • 43
    • 84896714737 scopus 로고    scopus 로고
    • Ionic protein-lipid interaction at the plasma membrane: What can the charge do?
    • Li L, Shi X, Guo X, Li H, Xu C, (2014). Ionic protein-lipid interaction at the plasma membrane: what can the charge do? Trends Biochem Sci 39: 130-140.
    • (2014) Trends Biochem Sci , vol.39 , pp. 130-140
    • Li, L.1    Shi, X.2    Guo, X.3    Li, H.4    Xu, C.5
  • 44
    • 33845505655 scopus 로고    scopus 로고
    • Curvature and hydrophobic forces drive oligomerization and modulate activity of rhodopsin in membranes
    • Botelho AV, Huber T, Sakmar TP, Brown MF, (2006). Curvature and hydrophobic forces drive oligomerization and modulate activity of rhodopsin in membranes. Biophys J 91: 4464-4477.
    • (2006) Biophys J , vol.91 , pp. 4464-4477
    • Botelho, A.V.1    Huber, T.2    Sakmar, T.P.3    Brown, M.F.4
  • 45
    • 12344330612 scopus 로고    scopus 로고
    • A study of the membrane-water interface region of membrane proteins
    • Granseth E, von Heijne G, Elofsson A, (2005). A study of the membrane-water interface region of membrane proteins. J Mol Biol 346: 377-385.
    • (2005) J Mol Biol , vol.346 , pp. 377-385
    • Granseth, E.1    Von Heijne, G.2    Elofsson, A.3
  • 46
    • 0026451081 scopus 로고
    • Intracellular signaling by hydrolysis of phospholipids and activation of protein kinase C
    • Nishizuka Y, (1992). Intracellular signaling by hydrolysis of phospholipids and activation of protein kinase C. Science 258: 607-614.
    • (1992) Science , vol.258 , pp. 607-614
    • Nishizuka, Y.1
  • 50
    • 48249095616 scopus 로고    scopus 로고
    • How translocons select transmembrane helices
    • White SH, von Heijne G, (2008). How translocons select transmembrane helices. Annu Rev Biophys 37: 23-42.
    • (2008) Annu Rev Biophys , vol.37 , pp. 23-42
    • White, S.H.1    Von Heijne, G.2
  • 52
    • 78049253482 scopus 로고    scopus 로고
    • Lateral opening of a translocon upon entry of protein suggests the mechanism of insertion into membranes
    • Egea PF, Stroud RM, (2010). Lateral opening of a translocon upon entry of protein suggests the mechanism of insertion into membranes. Proc Natl Acad Sci USA 107: 17182-17187.
    • (2010) Proc Natl Acad Sci USA , vol.107 , pp. 17182-17187
    • Egea, P.F.1    Stroud, R.M.2
  • 56
    • 4143101547 scopus 로고    scopus 로고
    • The machinery of membrane protein assembly
    • White SH, von Heijne G, (2004). The machinery of membrane protein assembly. Curr Opin Struct Biol 14: 397-404.
    • (2004) Curr Opin Struct Biol , vol.14 , pp. 397-404
    • White, S.H.1    Von Heijne, G.2
  • 57
    • 18544380083 scopus 로고    scopus 로고
    • Disulfide bridge formation between SecY and a translocating polypeptide localizes the translocation pore to the center of SecY
    • Cannon KS, Or E, Clemons WM, Shibata Y, Rapoport TA, (2005). Disulfide bridge formation between SecY and a translocating polypeptide localizes the translocation pore to the center of SecY. J Cell Biol 169: 219-225.
    • (2005) J Cell Biol , vol.169 , pp. 219-225
    • Cannon, K.S.1    Or, E.2    Clemons, W.M.3    Shibata, Y.4    Rapoport, T.A.5
  • 58
    • 0141992130 scopus 로고    scopus 로고
    • Cotranslational protein integration into the ER membrane is mediated by the binding of nascent chains to translocon proteins
    • McCormick PJ, Miao Y, Shao Y, Lin J, Johnson AE, (2003). Cotranslational protein integration into the ER membrane is mediated by the binding of nascent chains to translocon proteins. Mol Cell 12: 329-341.
    • (2003) Mol Cell , vol.12 , pp. 329-341
    • McCormick, P.J.1    Miao, Y.2    Shao, Y.3    Lin, J.4    Johnson, A.E.5
  • 59
    • 77950448361 scopus 로고    scopus 로고
    • Hydrophobically stabilized open state for the lateral gate of the sec translocon
    • Zhang B, Miller TF, (2010). Hydrophobically stabilized open state for the lateral gate of the sec translocon. Proc Natl Acad Sci USA 107: 5399-5404.
    • (2010) Proc Natl Acad Sci USA , vol.107 , pp. 5399-5404
    • Zhang, B.1    Miller, T.F.2
  • 61
    • 84866388574 scopus 로고    scopus 로고
    • Bacterial protein translocation requires only one copy of the SecY complex in vivo
    • Park E, Rapoport TA, (2012). Bacterial protein translocation requires only one copy of the SecY complex in vivo. J Cell Biol 198: 881-893.
    • (2012) J Cell Biol , vol.198 , pp. 881-893
    • Park, E.1    Rapoport, T.A.2
  • 62
    • 0037450802 scopus 로고    scopus 로고
    • Substrate-specific function of the translocon-associated protein complex during translocation across the ER membrane
    • Fons RD, Bogert BA, Hegde RS, (2003). Substrate-specific function of the translocon-associated protein complex during translocation across the ER membrane. J Cell Biol 160: 529-539.
    • (2003) J Cell Biol , vol.160 , pp. 529-539
    • Fons, R.D.1    Bogert, B.A.2    Hegde, R.S.3
  • 63
    • 0036906637 scopus 로고    scopus 로고
    • Different transmembrane domains associate with distinct endoplasmic reticulum components during membrane integration of a polytopic protein
    • Meacock SL, Lecomte FJ, Crawshaw SG, High S, (2002). Different transmembrane domains associate with distinct endoplasmic reticulum components during membrane integration of a polytopic protein. Mol Biol Cell 13: 4114-4129.
    • (2002) Mol Biol Cell , vol.13 , pp. 4114-4129
    • Meacock, S.L.1    Lecomte, F.J.2    Crawshaw, S.G.3    High, S.4
  • 64
    • 0032113448 scopus 로고    scopus 로고
    • Regulation of protein topology by transacting factors at the endoplasmic reticulum
    • Hegde RS, Voigt S, Lingappa VR, (1998). Regulation of protein topology by transacting factors at the endoplasmic reticulum. Mol Cell 2: 85-91.
    • (1998) Mol Cell , vol.2 , pp. 85-91
    • Hegde, R.S.1    Voigt, S.2    Lingappa, V.R.3
  • 65
    • 84901976635 scopus 로고    scopus 로고
    • How YidC inserts and folds proteins across a membrane
    • Dalbey RE, Kuhn A, (2014). How YidC inserts and folds proteins across a membrane. Nat Struct Mol Biol 21: 435-436.
    • (2014) Nat Struct Mol Biol , vol.21 , pp. 435-436
    • Dalbey, R.E.1    Kuhn, A.2
  • 66
    • 0026504192 scopus 로고
    • A protein of the endoplasmic reticulum involved early in polypeptide translocation
    • Gorlich D, Hartmann E, Prehn S, Rapoport TA, (1992). A protein of the endoplasmic reticulum involved early in polypeptide translocation. Nature 357: 47-52.
    • (1992) Nature , vol.357 , pp. 47-52
    • Gorlich, D.1    Hartmann, E.2    Prehn, S.3    Rapoport, T.A.4
  • 67
    • 0032489505 scopus 로고    scopus 로고
    • TRAM regulates the exposure of nascent secretory proteins to the cytosol during translocation into the endoplasmic reticulum
    • Hegde RS, Voigt S, Rapoport TA, Lingappa VR, (1998). TRAM regulates the exposure of nascent secretory proteins to the cytosol during translocation into the endoplasmic reticulum. Cell 92: 621-631.
    • (1998) Cell , vol.92 , pp. 621-631
    • Hegde, R.S.1    Voigt, S.2    Rapoport, T.A.3    Lingappa, V.R.4
  • 68
  • 69
    • 0012295328 scopus 로고
    • Purification of microsomal signal peptidase as a complex
    • Evans EA, Gilmore R, Blobel G, (1986). Purification of microsomal signal peptidase as a complex. Proc Natl Acad Sci USA 83: 581-585.
    • (1986) Proc Natl Acad Sci USA , vol.83 , pp. 581-585
    • Evans, E.A.1    Gilmore, R.2    Blobel, G.3
  • 70
    • 20744441520 scopus 로고    scopus 로고
    • Subunits of the translocon interact with components of the oligosaccharyl transferase complex
    • Chavan M, Yan A, Lennarz WJ, (2005). Subunits of the translocon interact with components of the oligosaccharyl transferase complex. J Biol Chem 280: 22917-22924.
    • (2005) J Biol Chem , vol.280 , pp. 22917-22924
    • Chavan, M.1    Yan, A.2    Lennarz, W.J.3
  • 71
    • 23044510444 scopus 로고    scopus 로고
    • Transmembrane helices before, during, and after insertion
    • White SH, von Heijne G, (2005). Transmembrane helices before, during, and after insertion. Curr Opin Struct Biol 15: 378-386.
    • (2005) Curr Opin Struct Biol , vol.15 , pp. 378-386
    • White, S.H.1    Von Heijne, G.2
  • 72
    • 4944228608 scopus 로고    scopus 로고
    • Topogenesis of membrane proteins at the endoplasmic reticulum
    • Higy M, Junne T, Spiess M, (2004). Topogenesis of membrane proteins at the endoplasmic reticulum. Biochemistry 43: 12716-12722.
    • (2004) Biochemistry , vol.43 , pp. 12716-12722
    • Higy, M.1    Junne, T.2    Spiess, M.3
  • 73
    • 0029738872 scopus 로고    scopus 로고
    • Experimentally determined hydrophobicity scale for proteins at membrane interfaces
    • Wimley WC, White SH, (1996). Experimentally determined hydrophobicity scale for proteins at membrane interfaces. Nat Struct Biol 3: 842-848.
    • (1996) Nat Struct Biol , vol.3 , pp. 842-848
    • Wimley, W.C.1    White, S.H.2
  • 74
    • 0030249150 scopus 로고    scopus 로고
    • Threshold hydrophobicity dictates helical conformations of peptides in membrane environments
    • Liu LP, Li SC, Goto NK, Deber CM, (1996). Threshold hydrophobicity dictates helical conformations of peptides in membrane environments. Biopolymers 39: 465-470.
    • (1996) Biopolymers , vol.39 , pp. 465-470
    • Liu, L.P.1    Li, S.C.2    Goto, N.K.3    Deber, C.M.4
  • 75
    • 79961238544 scopus 로고    scopus 로고
    • Apolar surface area determines the efficiency of translocon-mediated membrane-protein integration into the endoplasmic reticulum
    • Ojemalm K, Higuchi T, Jiang Y, Langel U, Nilsson I, White SH, Suga H, von Heijne G, (2011). Apolar surface area determines the efficiency of translocon-mediated membrane-protein integration into the endoplasmic reticulum. Proc Natl Acad Sci USA 108: E359-E364.
    • (2011) Proc Natl Acad Sci USA , vol.108 , pp. E359-E364
    • Ojemalm, K.1    Higuchi, T.2    Jiang, Y.3    Langel, U.4    Nilsson, I.5    White, S.H.6    Suga, H.7    Von Heijne, G.8
  • 76
    • 84906320078 scopus 로고    scopus 로고
    • Why is the biological hydrophobicity scale more accurate than earlier experimental hydrophobicity scales?
    • Peters C, Elofsson A, (2014). Why is the biological hydrophobicity scale more accurate than earlier experimental hydrophobicity scales? Proteins 82: 2190-2198.
    • (2014) Proteins , vol.82 , pp. 2190-2198
    • Peters, C.1    Elofsson, A.2
  • 78
    • 0032509153 scopus 로고    scopus 로고
    • Breaking the camel's back: Proline-induced turns in a model transmembrane helix
    • Nilsson I, von Heijne G, (1998). Breaking the camel's back: Proline-induced turns in a model transmembrane helix. J Mol Biol 284: 1185-1189.
    • (1998) J Mol Biol , vol.284 , pp. 1185-1189
    • Nilsson, I.1    Von Heijne, G.2
  • 79
    • 57349168025 scopus 로고    scopus 로고
    • Molecular code for protein insertion in the endoplasmic reticulum membrane is similar for N(in)-C(out) and N(out)-C(in) transmembrane helices
    • Lundin C, Kim H, Nilsson I, White SH, von Heijne G, (2008). Molecular code for protein insertion in the endoplasmic reticulum membrane is similar for N(in)-C(out) and N(out)-C(in) transmembrane helices. Proc Natl Acad Sci USA 105: 15702-15707.
    • (2008) Proc Natl Acad Sci USA , vol.105 , pp. 15702-15707
    • Lundin, C.1    Kim, H.2    Nilsson, I.3    White, S.H.4    Von Heijne, G.5
  • 80
    • 84879969808 scopus 로고    scopus 로고
    • Quantitative analysis of SecYEG-mediated insertion of transmembrane α-helices into the bacterial inner membrane
    • Ojemalm K, Botelho SC, Studle C, von Heijne G, (2013). Quantitative analysis of SecYEG-mediated insertion of transmembrane α-helices into the bacterial inner membrane. J Mol Biol 425: 2813-2822.
    • (2013) J Mol Biol , vol.425 , pp. 2813-2822
    • Ojemalm, K.1    Botelho, S.C.2    Studle, C.3    Von Heijne, G.4
  • 81
    • 60849083215 scopus 로고    scopus 로고
    • Analysis of transmembrane helix integration in the endoplasmic reticulum in S. Cerevisiae
    • Hessa T, Reithinger JH, von Heijne G, Kim H, (2009). Analysis of transmembrane helix integration in the endoplasmic reticulum in S. cerevisiae. J Mol Biol 386: 1222-1228.
    • (2009) J Mol Biol , vol.386 , pp. 1222-1228
    • Hessa, T.1    Reithinger, J.H.2    Von Heijne, G.3    Kim, H.4
  • 82
    • 0035795721 scopus 로고    scopus 로고
    • Amino acid distributions in integral membrane protein structures
    • Ulmschneider MB, Sansom MS, (2001). Amino acid distributions in integral membrane protein structures. Biochim Biophys Acta 1512: 1-14.
    • (2001) Biochim Biophys Acta , vol.1512 , pp. 1-14
    • Ulmschneider, M.B.1    Sansom, M.S.2
  • 83
    • 24644490119 scopus 로고    scopus 로고
    • Comparative analysis of amino acid distributions in integral membrane proteins from 107 genomes
    • Nilsson J, Persson B, von Heijne G, (2005). Comparative analysis of amino acid distributions in integral membrane proteins from 107 genomes. Proteins 60: 606-616.
    • (2005) Proteins , vol.60 , pp. 606-616
    • Nilsson, J.1    Persson, B.2    Von Heijne, G.3
  • 85
    • 2342544065 scopus 로고    scopus 로고
    • Snorkeling preferences foster an amino acid composition bias in transmembrane helices
    • Chamberlain AK, Lee Y, Kim S, Bowie JU, (2004). Snorkeling preferences foster an amino acid composition bias in transmembrane helices. J Mol Biol 339: 471-479.
    • (2004) J Mol Biol , vol.339 , pp. 471-479
    • Chamberlain, A.K.1    Lee, Y.2    Kim, S.3    Bowie, J.U.4
  • 87
    • 0032509124 scopus 로고    scopus 로고
    • Positively and negatively charged residues have different effects on the position in the membrane of a model transmembrane helix
    • Monne M, Nilsson I, Johansson M, Elmhed N, von Heijne G, (1998). Positively and negatively charged residues have different effects on the position in the membrane of a model transmembrane helix. J Mol Biol 284: 1177-1183.
    • (1998) J Mol Biol , vol.284 , pp. 1177-1183
    • Monne, M.1    Nilsson, I.2    Johansson, M.3    Elmhed, N.4    Von Heijne, G.5
  • 88
    • 0033587583 scopus 로고    scopus 로고
    • An aspartate residue at the extracellular boundary of TMII and an arginine residue in TMVII of the gastrin-releasing peptide receptor interact to facilitate heterotrimeric G protein coupling
    • Donohue PJ, Sainz E, Akeson M, Kroog GS, Mantey SA, Battey JF, Jensen RT, Northup JK, (1999). An aspartate residue at the extracellular boundary of TMII and an arginine residue in TMVII of the gastrin-releasing peptide receptor interact to facilitate heterotrimeric G protein coupling. Biochemistry 38: 9366-9372.
    • (1999) Biochemistry , vol.38 , pp. 9366-9372
    • Donohue, P.J.1    Sainz, E.2    Akeson, M.3    Kroog, G.S.4    Mantey, S.A.5    Battey, J.F.6    Jensen, R.T.7    Northup, J.K.8
  • 89
    • 0026439214 scopus 로고
    • Functional interactions between putative intramembrane charged residues in the lactose permease of Escherichia coli. Proc
    • Sahin-Toth M, Dunten RL, Gonzalez A, Kaback HR, (1992). Functional interactions between putative intramembrane charged residues in the lactose permease of Escherichia coli. Proc Natl Acad Sci USA 89: 10547-10551.
    • (1992) Natl Acad Sci USA , vol.89 , pp. 10547-10551
    • Sahin-Toth, M.1    Dunten, R.L.2    Gonzalez, A.3    Kaback, H.R.4
  • 90
    • 0026529067 scopus 로고
    • Different positively charged amino acids have similar effects on the topology of a polytopic transmembrane protein in Escherichia coli
    • Andersson H, Bakker E, von Heijne G, (1992). Different positively charged amino acids have similar effects on the topology of a polytopic transmembrane protein in Escherichia coli. J Biol Chem 267: 1491-1495.
    • (1992) J Biol Chem , vol.267 , pp. 1491-1495
    • Andersson, H.1    Bakker, E.2    Von Heijne, G.3
  • 91
    • 0025015646 scopus 로고
    • Fine-tuning the topology of a polytopic membrane protein: Role of positively and negatively charged amino acids
    • Nilsson I, von Heijne G, (1990). Fine-tuning the topology of a polytopic membrane protein: role of positively and negatively charged amino acids. Cell 62: 1135-1141.
    • (1990) Cell , vol.62 , pp. 1135-1141
    • Nilsson, I.1    Von Heijne, G.2
  • 92
    • 0032540320 scopus 로고    scopus 로고
    • The proton motive force, acting on acidic residues, promotes translocation of amino-terminal domains of membrane proteins when the hydrophobicity of the translocation signal is low
    • Delgado-Partin VM, Dalbey RE, (1998). The proton motive force, acting on acidic residues, promotes translocation of amino-terminal domains of membrane proteins when the hydrophobicity of the translocation signal is low. J Biol Chem 273: 9927-9934.
    • (1998) J Biol Chem , vol.273 , pp. 9927-9934
    • Delgado-Partin, V.M.1    Dalbey, R.E.2
  • 93
    • 0033584852 scopus 로고    scopus 로고
    • A single negatively charged residue affects the orientation of a membrane protein in the inner membrane of Escherichia coli only when it is located adjacent to a transmembrane domain
    • Rutz C, Rosenthal W, Schulein R, (1999). A single negatively charged residue affects the orientation of a membrane protein in the inner membrane of Escherichia coli only when it is located adjacent to a transmembrane domain. J Biol Chem 274: 33757-33763.
    • (1999) J Biol Chem , vol.274 , pp. 33757-33763
    • Rutz, C.1    Rosenthal, W.2    Schulein, R.3
  • 94
    • 0032987478 scopus 로고    scopus 로고
    • Membrane protein folding and stability: Physical principles
    • White SH, Wimley WC, (1999). Membrane protein folding and stability: physical principles. Annu Rev Biophys Biomol Struct 28: 319-365.
    • (1999) Annu Rev Biophys Biomol Struct , vol.28 , pp. 319-365
    • White, S.H.1    Wimley, W.C.2
  • 95
    • 0034284386 scopus 로고    scopus 로고
    • How proteins adapt to a membrane-water interface
    • Killian JA, von Heijne G, (2000). How proteins adapt to a membrane-water interface. Trends Biochem Sci 25: 429-434.
    • (2000) Trends Biochem Sci , vol.25 , pp. 429-434
    • Killian, J.A.1    Von Heijne, G.2
  • 96
    • 0033609498 scopus 로고    scopus 로고
    • The aromatic residues trp and phe have different effects on the positioning of a transmembrane helix in the microsomal membrane
    • Braun P, von Heijne G, (1999). The aromatic residues trp and phe have different effects on the positioning of a transmembrane helix in the microsomal membrane Biochemistry 38: 9778-9782.
    • (1999) Biochemistry , vol.38 , pp. 9778-9782
    • Braun, P.1    Von Heijne, G.2
  • 97
    • 0034327611 scopus 로고    scopus 로고
    • Hinges, swivels and switches: The role of prolines in signalling via transmembrane alpha-helices
    • Sansom MS, Weinstein H, (2000). Hinges, swivels and switches: the role of prolines in signalling via transmembrane alpha-helices. Trends Pharmacol Sci 21: 445-451.
    • (2000) Trends Pharmacol Sci , vol.21 , pp. 445-451
    • Sansom, M.S.1    Weinstein, H.2
  • 98
    • 33746361201 scopus 로고    scopus 로고
    • Structural classification and prediction of reentrant regions in alpha-helical transmembrane proteins: Application to complete genomes
    • Viklund H, Granseth E, Elofsson A, (2006). Structural classification and prediction of reentrant regions in alpha-helical transmembrane proteins: application to complete genomes. J Mol Biol 361: 591-603.
    • (2006) J Mol Biol , vol.361 , pp. 591-603
    • Viklund, H.1    Granseth, E.2    Elofsson, A.3
  • 99
    • 26444611461 scopus 로고    scopus 로고
    • Transmembrane glycine zippers: Physiological and pathological roles in membrane proteins
    • Kim S, Jeon TJ, Oberai A, Yang D, Schmidt JJ, Bowie JU, (2005). Transmembrane glycine zippers: physiological and pathological roles in membrane proteins. Proc Natl Acad Sci USA 102: 14278-14283.
    • (2005) Proc Natl Acad Sci USA , vol.102 , pp. 14278-14283
    • Kim, S.1    Jeon, T.J.2    Oberai, A.3    Yang, D.4    Schmidt, J.J.5    Bowie, J.U.6
  • 100
    • 4143085058 scopus 로고    scopus 로고
    • Folding of helical membrane proteins: The role of polar, GxxxG-like and proline motifs
    • Senes A, Engel DE, DeGrado WF, (2004). Folding of helical membrane proteins: the role of polar, GxxxG-like and proline motifs. Curr Opin Struct Biol 14: 465-479.
    • (2004) Curr Opin Struct Biol , vol.14 , pp. 465-479
    • Senes, A.1    Engel, D.E.2    DeGrado, W.F.3
  • 101
    • 0000651660 scopus 로고
    • The distribution of positively charged residues in bacterial inner membrane proteins correlates with the trans-membrane topology
    • Heijne G, (1986). The distribution of positively charged residues in bacterial inner membrane proteins correlates with the trans-membrane topology. EMBO J 5: 3021-3027.
    • (1986) EMBO J , vol.5 , pp. 3021-3027
    • Heijne, G.1
  • 102
    • 0031954925 scopus 로고    scopus 로고
    • Genome-wide analysis of integral membrane proteins from eubacterial, archaean, and eukaryotic organisms
    • Wallin E, von Heijne G, (1998). Genome-wide analysis of integral membrane proteins from eubacterial, archaean, and eukaryotic organisms. Protein Sci 7: 1029-1038.
    • (1998) Protein Sci , vol.7 , pp. 1029-1038
    • Wallin, E.1    Von Heijne, G.2
  • 103
    • 41949125627 scopus 로고    scopus 로고
    • Contribution of positively charged flanking residues to the insertion of transmembrane helices into the endoplasmic reticulum
    • Lerch-Bader M, Lundin C, Kim H, Nilsson I, von Heijne G, (2008). Contribution of positively charged flanking residues to the insertion of transmembrane helices into the endoplasmic reticulum. Proc Natl Acad Sci USA 105: 4127-4132.
    • (2008) Proc Natl Acad Sci USA , vol.105 , pp. 4127-4132
    • Lerch-Bader, M.1    Lundin, C.2    Kim, H.3    Nilsson, I.4    Von Heijne, G.5
  • 104
    • 0027263346 scopus 로고
    • Positively charged amino acids placed next to a signal sequence block protein translocation more efficiently in Escherichia coli than in mammalian microsomes
    • Johansson M, Nilsson I, von Heijne G, (1993). Positively charged amino acids placed next to a signal sequence block protein translocation more efficiently in Escherichia coli than in mammalian microsomes. Mol Gen Genet 239: 251-256.
    • (1993) Mol Gen Genet , vol.239 , pp. 251-256
    • Johansson, M.1    Nilsson, I.2    Von Heijne, G.3
  • 105
    • 0031843725 scopus 로고    scopus 로고
    • The positive inside rule is not determined by the polarity of the delta psi (transmembrane electrical potential)
    • van de Vossenberg JL, Albers SV, van der Does C, Driessen AJ, van Klompenburg W, (1998) The positive inside rule is not determined by the polarity of the delta psi (transmembrane electrical potential). Mol Microbiol 29: 1125-1127.
    • (1998) Mol Microbiol , vol.29 , pp. 1125-1127
    • Van De Vossenberg, J.L.1    Albers, S.V.2    Van Der Does, C.3    Driessen, A.J.4    Van Klompenburg, W.5
  • 106
    • 9144247030 scopus 로고    scopus 로고
    • The role of lipids in membrane insertion and translocation of bacterial proteins
    • van Dalen A, de Kruijff B, (2004). The role of lipids in membrane insertion and translocation of bacterial proteins. Biochim Biophys Acta 1694: 97-109.
    • (2004) Biochim Biophys Acta , vol.1694 , pp. 97-109
    • Van Dalen, A.1    De Kruijff, B.2
  • 107
    • 0025142363 scopus 로고
    • Initial steps in protein membrane insertion. Bacteriophage m13 procoat protein binds to the membrane surface by electrostatic interaction
    • Gallusser A, Kuhn A, (1990). Initial steps in protein membrane insertion. Bacteriophage m13 procoat protein binds to the membrane surface by electrostatic interaction. EMBO J 9: 2723-2729.
    • (1990) EMBO J , vol.9 , pp. 2723-2729
    • Gallusser, A.1    Kuhn, A.2
  • 108
    • 84873100800 scopus 로고    scopus 로고
    • A retrospective: Use of Escherichia coli as a vehicle to study phospholipid synthesis and function
    • Dowhan W, (2013). A retrospective: use of Escherichia coli as a vehicle to study phospholipid synthesis and function. BBA 1831: 471-494.
    • (2013) BBA , vol.1831 , pp. 471-494
    • Dowhan, W.1
  • 109
    • 1542313960 scopus 로고    scopus 로고
    • Sec61p contributes to signal sequence orientation according to the positive-inside rule
    • Goder V, Junne T, Spiess M, (2004). Sec61p contributes to signal sequence orientation according to the positive-inside rule. Mol Biol Cell 15: 1470-1478.
    • (2004) Mol Biol Cell , vol.15 , pp. 1470-1478
    • Goder, V.1    Junne, T.2    Spiess, M.3
  • 110
    • 36349034451 scopus 로고    scopus 로고
    • Mutations in the Sec61p channel affecting signal sequence recognition and membrane protein topology
    • Junne T, Schwede T, Goder V, Spiess M, (2007). Mutations in the Sec61p channel affecting signal sequence recognition and membrane protein topology. J Biol Chem 282: 33201-33209.
    • (2007) J Biol Chem , vol.282 , pp. 33201-33209
    • Junne, T.1    Schwede, T.2    Goder, V.3    Spiess, M.4
  • 111
    • 0025249842 scopus 로고
    • Membrane protein folding and oligomerization: The two-stage model
    • Popot JL, Engelman DM, (1990) Membrane protein folding and oligomerization: the two-stage model. Biochemistry 29: 4031-4037.
    • (1990) Biochemistry , vol.29 , pp. 4031-4037
    • Popot, J.L.1    Engelman, D.M.2
  • 112
    • 28444488355 scopus 로고    scopus 로고
    • Solving the membrane protein folding problem
    • Bowie JU, (2005). Solving the membrane protein folding problem. Nature 438: 581-589.
    • (2005) Nature , vol.438 , pp. 581-589
    • Bowie, J.U.1
  • 113
    • 79959979273 scopus 로고    scopus 로고
    • A flip turn for membrane protein insertion
    • Shao S, Hegde RS, (2011). A flip turn for membrane protein insertion. Cell 146: 13-15.
    • (2011) Cell , vol.146 , pp. 13-15
    • Shao, S.1    Hegde, R.S.2
  • 115
    • 0032185234 scopus 로고    scopus 로고
    • Forced transmembrane orientation of hydrophilic polypeptide segments in multispanning membrane proteins
    • Ota K, Sakaguchi M, von Heijne G, Hamasaki N, Mihara K, (1998). Forced transmembrane orientation of hydrophilic polypeptide segments in multispanning membrane proteins. Mol Cell 2: 495-503.
    • (1998) Mol Cell , vol.2 , pp. 495-503
    • Ota, K.1    Sakaguchi, M.2    Von Heijne, G.3    Hamasaki, N.4    Mihara, K.5
  • 116
    • 27144549973 scopus 로고    scopus 로고
    • Sequential triage of transmembrane segments by Sec61alpha during biogenesis of a native multispanning membrane protein
    • Sadlish H, Pitonzo D, Johnson AE, Skach WR, (2005). Sequential triage of transmembrane segments by Sec61alpha during biogenesis of a native multispanning membrane protein. Nat Struct Mol Biol 12: 870-878.
    • (2005) Nat Struct Mol Biol , vol.12 , pp. 870-878
    • Sadlish, H.1    Pitonzo, D.2    Johnson, A.E.3    Skach, W.R.4
  • 117
    • 0029060799 scopus 로고
    • Artificial transmembrane segments. Requirements for stop transfer and polypeptide orientation
    • Chen H, Kendall DA, (1995). Artificial transmembrane segments. Requirements for stop transfer and polypeptide orientation. J Biol Chem 270: 14115-14122.
    • (1995) J Biol Chem , vol.270 , pp. 14115-14122
    • Chen, H.1    Kendall, D.A.2
  • 118
    • 0030919649 scopus 로고    scopus 로고
    • Multiple determinants direct the orientation of signal-anchor proteins: The topogenic role of the hydrophobic signal domain
    • Wahlberg JM, Spiess M, (1997) Multiple determinants direct the orientation of signal-anchor proteins: the topogenic role of the hydrophobic signal domain. J Cell Biol 137: 555-562.
    • (1997) J Cell Biol , vol.137 , pp. 555-562
    • Wahlberg, J.M.1    Spiess, M.2
  • 119
    • 0039005869 scopus 로고    scopus 로고
    • The topogenic contribution of uncharged amino acids on signal sequence orientation in the endoplasmic reticulum
    • Rosch K, Naeher D, Laird V, Goder V, Spiess M, (2000). The topogenic contribution of uncharged amino acids on signal sequence orientation in the endoplasmic reticulum. J Biol Chem 275: 14916-14922.
    • (2000) J Biol Chem , vol.275 , pp. 14916-14922
    • Rosch, K.1    Naeher, D.2    Laird, V.3    Goder, V.4    Spiess, M.5
  • 120
    • 0042313962 scopus 로고    scopus 로고
    • Molecular mechanism of signal sequence orientation in the endoplasmic reticulum
    • Goder V, Spiess M, (2003). Molecular mechanism of signal sequence orientation in the endoplasmic reticulum. EMBO J 22: 3645-3653.
    • (2003) EMBO J , vol.22 , pp. 3645-3653
    • Goder, V.1    Spiess, M.2
  • 121
    • 0024268344 scopus 로고
    • Introduction of basic amino acid residues after the signal peptide inhibits protein translocation across the cytoplasmic membrane of Escherichia coli. Relation to the orientation of membrane proteins
    • Yamane K, Mizushima S, (1988). Introduction of basic amino acid residues after the signal peptide inhibits protein translocation across the cytoplasmic membrane of Escherichia coli. Relation to the orientation of membrane proteins. J Biol Chem 263: 19690-19696.
    • (1988) J Biol Chem , vol.263 , pp. 19690-19696
    • Yamane, K.1    Mizushima, S.2
  • 122
    • 0032502747 scopus 로고    scopus 로고
    • Refolding of bacteriorhodopsin from expressed polypeptide fragments
    • Marti T, (1998). Refolding of bacteriorhodopsin from expressed polypeptide fragments. J Biol Chem 273: 9312-9322.
    • (1998) J Biol Chem , vol.273 , pp. 9312-9322
    • Marti, T.1
  • 123
    • 0030838729 scopus 로고    scopus 로고
    • Reconstitution of functional voltage-gated chloride channels from complementary fragments of CLC-1
    • Schmidt-Rose T, Jentsch TJ, (1997). Reconstitution of functional voltage-gated chloride channels from complementary fragments of CLC-1. J Biol Chem 272: 20515-20521.
    • (1997) J Biol Chem , vol.272 , pp. 20515-20521
    • Schmidt-Rose, T.1    Jentsch, T.J.2
  • 124
    • 68249144241 scopus 로고    scopus 로고
    • Similar energetic contributions of packing in the core of membrane and water-soluble proteins
    • Joh NH, Oberai A, Yang D, Whitelegge JP, Bowie JU, (2009) Similar energetic contributions of packing in the core of membrane and water-soluble proteins. J Am Chem Soc 131: 10846-10847.
    • (2009) J Am Chem Soc , vol.131 , pp. 10846-10847
    • Joh, N.H.1    Oberai, A.2    Yang, D.3    Whitelegge, J.P.4    Bowie, J.U.5
  • 125
    • 70449555146 scopus 로고    scopus 로고
    • Structural imperatives impose diverse evolutionary constraints on helical membrane proteins
    • Oberai A, Joh NH, Pettit FK, Bowie JU, (2009) Structural imperatives impose diverse evolutionary constraints on helical membrane proteins. Proc Natl Acad Sci USA 106: 17747-17750.
    • (2009) Proc Natl Acad Sci USA , vol.106 , pp. 17747-17750
    • Oberai, A.1    Joh, N.H.2    Pettit, F.K.3    Bowie, J.U.4
  • 126
    • 0037019829 scopus 로고    scopus 로고
    • CH.O hydrogen bonds at protein-protein interfaces
    • Jiang L, Lai L, (2002). CH.O hydrogen bonds at protein-protein interfaces. J Biol Chem 277: 37732-37740.
    • (2002) J Biol Chem , vol.277 , pp. 37732-37740
    • Jiang, L.1    Lai, L.2
  • 127
    • 0035971221 scopus 로고    scopus 로고
    • Strength of the calpha H.O hydrogen bond of amino acid residues
    • Scheiner S, Kar T, Gu Y, (2001). Strength of the calpha H.O hydrogen bond of amino acid residues. J Biol Chem 276: 9832-9837.
    • (2001) J Biol Chem , vol.276 , pp. 9832-9837
    • Scheiner, S.1    Kar, T.2    Gu, Y.3
  • 128
    • 2342449189 scopus 로고    scopus 로고
    • Experimental measurement of the strength of a C alpha-H.O bond in a lipid bilayer
    • Arbely E, Arkin IT, (2004). Experimental measurement of the strength of a C alpha-H.O bond in a lipid bilayer. J Am Chem Soc 126: 5362-5363.
    • (2004) J Am Chem Soc , vol.126 , pp. 5362-5363
    • Arbely, E.1    Arkin, I.T.2
  • 130
    • 0035979146 scopus 로고    scopus 로고
    • The calpha - H.O hydrogen bond: A determinant of stability and specificity in transmembrane helix interactions
    • Senes A, Ubarretxena-Belandia I, Engelman DM, (2001). The calpha-H.O hydrogen bond: a determinant of stability and specificity in transmembrane helix interactions. Proc Natl Acad Sci USA 98: 9056-9061.
    • (2001) Proc Natl Acad Sci USA , vol.98 , pp. 9056-9061
    • Senes, A.1    Ubarretxena-Belandia, I.2    Engelman, D.M.3
  • 131
    • 44049094995 scopus 로고    scopus 로고
    • Hydrogen-bonding and packing features of membrane proteins: Functional implications
    • Hildebrand PW, Gunther S, Goede A, Forrest L, Frommel C, Preissner R, (2008) Hydrogen-bonding and packing features of membrane proteins: functional implications. Biophys J 94: 1945-1953.
    • (2008) Biophys J , vol.94 , pp. 1945-1953
    • Hildebrand, P.W.1    Gunther, S.2    Goede, A.3    Forrest, L.4    Frommel, C.5    Preissner, R.6
  • 132
    • 33748602095 scopus 로고    scopus 로고
    • Molecular mechanisms of aquaporin biogenesis by the endoplasmic reticulum sec61 translocon
    • Pitonzo D, Skach WR, (2006). Molecular mechanisms of aquaporin biogenesis by the endoplasmic reticulum sec61 translocon. Biochim Biophys Acta 1758: 976-988.
    • (2006) Biochim Biophys Acta , vol.1758 , pp. 976-988
    • Pitonzo, D.1    Skach, W.R.2
  • 133
    • 34249683488 scopus 로고    scopus 로고
    • Membrane protein structure: Prediction versus reality
    • Elofsson A, von Heijne G, (2007) Membrane protein structure: prediction versus reality. Annu Rev Biochem 76: 125-140.
    • (2007) Annu Rev Biochem , vol.76 , pp. 125-140
    • Elofsson, A.1    Von Heijne, G.2
  • 135
    • 78649770531 scopus 로고    scopus 로고
    • Why are polar residues within the membrane core evolutionary conserved?
    • Illergard K, Kauko A, Elofsson A, (2011). Why are polar residues within the membrane core evolutionary conserved?. Proteins 79: 79-91. -
    • (2011) Proteins , vol.79 , pp. 79-91
    • Illergard, K.1    Kauko, A.2    Elofsson, A.3
  • 136
    • 84868317374 scopus 로고    scopus 로고
    • Lipid-dependent generation of dual topology for a membrane protein
    • Bogdanov M, Dowhan W, (2012). Lipid-dependent generation of dual topology for a membrane protein. J Biol Chem 287: 37939-37948.
    • (2012) J Biol Chem , vol.287 , pp. 37939-37948
    • Bogdanov, M.1    Dowhan, W.2
  • 137
    • 33746644754 scopus 로고    scopus 로고
    • Membrane proteins shape up: Understanding in vitro folding
    • Booth PJ, Curnow P, (2006). Membrane proteins shape up: understanding in vitro folding. Curr Opin Struct Biol 16: 480-488.
    • (2006) Curr Opin Struct Biol , vol.16 , pp. 480-488
    • Booth, P.J.1    Curnow, P.2
  • 138
    • 84857641142 scopus 로고    scopus 로고
    • Folding and stability of membrane transport proteins in vitro
    • Harris NJ, Booth PJ, (2012). Folding and stability of membrane transport proteins in vitro. Biochim Biophys Acta 1818: 1055-1066.
    • (2012) Biochim Biophys Acta , vol.1818 , pp. 1055-1066
    • Harris, N.J.1    Booth, P.J.2
  • 139
    • 17744395499 scopus 로고    scopus 로고
    • Biogenesis of CFTR and other polytopic membrane proteins: New roles for the ribosome-translocon complex
    • Sadlish H, Skach WR, (2004). Biogenesis of CFTR and other polytopic membrane proteins: new roles for the ribosome-translocon complex. J Membr Biol 202: 115-126.
    • (2004) J Membr Biol , vol.202 , pp. 115-126
    • Sadlish, H.1    Skach, W.R.2
  • 140
    • 0042815085 scopus 로고    scopus 로고
    • Cooperation of transmembrane segments during the integration of a double-spanning protein into the ER membrane
    • Heinrich SU, Rapoport TA, (2003). Cooperation of transmembrane segments during the integration of a double-spanning protein into the ER membrane. EMBO J 22: 3654-3663.
    • (2003) EMBO J , vol.22 , pp. 3654-3663
    • Heinrich, S.U.1    Rapoport, T.A.2
  • 141
    • 0037039368 scopus 로고    scopus 로고
    • Integration of Shaker-type K+ channel, kat1, into the endoplasmic reticulum membrane: Synergistic insertion of voltage-sensing segments, S3-s4, and independent insertion of pore-forming segments, S5-P-s6. Proc
    • Sato Y, Sakaguchi M, Goshima S, Nakamura T, Uozumi N, (2002). Integration of Shaker-type K+ channel, kat1, into the endoplasmic reticulum membrane: synergistic insertion of voltage-sensing segments, S3-s4, and independent insertion of pore-forming segments, S5-P-s6. Proc Natl Acad Sci USA 99: 60-65.
    • (2002) Natl Acad Sci USA , vol.99 , pp. 60-65
    • Sato, Y.1    Sakaguchi, M.2    Goshima, S.3    Nakamura, T.4    Uozumi, N.5
  • 142
    • 44649159957 scopus 로고    scopus 로고
    • Coils in the membrane core are conserved and functionally important
    • Kauko A, Illergard K, Elofsson A, (2008). Coils in the membrane core are conserved and functionally important. J Mol Biol 380: 170-180.
    • (2008) J Mol Biol , vol.380 , pp. 170-180
    • Kauko, A.1    Illergard, K.2    Elofsson, A.3
  • 143
    • 34547650465 scopus 로고    scopus 로고
    • A novel tripartite motif involved in aquaporin topogenesis, monomer folding and tetramerization
    • Buck TM, Wagner J, Grund S, Skach WR, (2007). A novel tripartite motif involved in aquaporin topogenesis, monomer folding and tetramerization. Nat Struct Mol Biol 14: 762-769.
    • (2007) Nat Struct Mol Biol , vol.14 , pp. 762-769
    • Buck, T.M.1    Wagner, J.2    Grund, S.3    Skach, W.R.4
  • 144
    • 33750498869 scopus 로고    scopus 로고
    • Asn- and ASP-mediated interactions between transmembrane helices during translocon-mediated membrane protein assembly
    • Meindl-Beinker NM, Lundin C, Nilsson I, White SH, von Heijne G, (2006). Asn- and Asp-mediated interactions between transmembrane helices during translocon-mediated membrane protein assembly. EMBO Rep 7: 1111-1116.
    • (2006) EMBO Rep , vol.7 , pp. 1111-1116
    • Meindl-Beinker, N.M.1    Lundin, C.2    Nilsson, I.3    White, S.H.4    Von Heijne, G.5
  • 145
    • 34347249218 scopus 로고    scopus 로고
    • Contribution of hydrophobic and electrostatic interactions to the membrane integration of the shaker K+ channel voltage sensor domain
    • Zhang L, Sato Y, Hessa T, von Heijne G, Lee JK, Kodama I, Sakaguchi M, Uozumi N, (2007). Contribution of hydrophobic and electrostatic interactions to the membrane integration of the shaker K+ channel voltage sensor domain. Proc Natl Acad Sci USA 104: 8263-8268.
    • (2007) Proc Natl Acad Sci USA , vol.104 , pp. 8263-8268
    • Zhang, L.1    Sato, Y.2    Hessa, T.3    Von Heijne, G.4    Lee, J.K.5    Kodama, I.6    Sakaguchi, M.7    Uozumi, N.8
  • 146
    • 84857439394 scopus 로고    scopus 로고
    • Orientational preferences of neighboring helices can drive ER insertion of a marginally hydrophobic transmembrane helix
    • Ojemalm K, Halling KK, Nilsson I, von Heijne G, (2012). Orientational preferences of neighboring helices can drive ER insertion of a marginally hydrophobic transmembrane helix. Mol Cell 45: 529-540.
    • (2012) Mol Cell , vol.45 , pp. 529-540
    • Ojemalm, K.1    Halling, K.K.2    Nilsson, I.3    Von Heijne, G.4
  • 148
    • 0028318283 scopus 로고
    • Biogenesis and transmembrane topology of the chip28 water channel at the endoplasmic reticulum
    • Skach WR, Shi LB, Calayag MC, Frigeri A, Lingappa VR, Verkman AS, (1994). Biogenesis and transmembrane topology of the chip28 water channel at the endoplasmic reticulum. J Cell Biol 125: 803-815.
    • (1994) J Cell Biol , vol.125 , pp. 803-815
    • Skach, W.R.1    Shi, L.B.2    Calayag, M.C.3    Frigeri, A.4    Lingappa, V.R.5    Verkman, A.S.6
  • 149
    • 0034492193 scopus 로고    scopus 로고
    • Reorientation of aquaporin-1 topology during maturation in the endoplasmic reticulum
    • Lu Y, Turnbull IR, Bragin A, Carveth K, Verkman AS, Skach WR, (2000). Reorientation of aquaporin-1 topology during maturation in the endoplasmic reticulum. Mol Biol Cell 11: 2973-2985.
    • (2000) Mol Biol Cell , vol.11 , pp. 2973-2985
    • Lu, Y.1    Turnbull, I.R.2    Bragin, A.3    Carveth, K.4    Verkman, A.S.5    Skach, W.R.6
  • 150
    • 0027976658 scopus 로고
    • Membrane topology of aquaporin CHIP. Analysis of functional epitope-scanning mutants by vectorial proteolysis
    • Preston GM, Jung JS, Guggino WB, Agre P, (1994). Membrane topology of aquaporin CHIP. Analysis of functional epitope-scanning mutants by vectorial proteolysis. J Biol Chem 269: 1668-1673.
    • (1994) J Biol Chem , vol.269 , pp. 1668-1673
    • Preston, G.M.1    Jung, J.S.2    Guggino, W.B.3    Agre, P.4
  • 151
    • 12844283314 scopus 로고    scopus 로고
    • Differential stability of biogenesis intermediates reveals a common pathway for aquaporin-1 topological maturation
    • Buck TM, Skach WR, (2005). Differential stability of biogenesis intermediates reveals a common pathway for aquaporin-1 topological maturation. J Biol Chem 280: 261-269.
    • (2005) J Biol Chem , vol.280 , pp. 261-269
    • Buck, T.M.1    Skach, W.R.2
  • 152
    • 0034602391 scopus 로고    scopus 로고
    • Identification of sequence determinants that direct different intracellular folding pathways for aquaporin-1 and aquaporin-4
    • Foster W, Helm A, Turnbull I, Gulati H, Yang B, Verkman AS, Skach WR, (2000). Identification of sequence determinants that direct different intracellular folding pathways for aquaporin-1 and aquaporin-4. J Biol Chem 275: 34157-34165.
    • (2000) J Biol Chem , vol.275 , pp. 34157-34165
    • Foster, W.1    Helm, A.2    Turnbull, I.3    Gulati, H.4    Yang, B.5    Verkman, A.S.6    Skach, W.R.7
  • 153
    • 84899550455 scopus 로고    scopus 로고
    • Quantifying absolute protein synthesis rates reveals principles underlying allocation of cellular resources
    • Li GW, Burkhardt D, Gross C, Weissman JS, (2014). Quantifying absolute protein synthesis rates reveals principles underlying allocation of cellular resources. Cell 157: 624-635.
    • (2014) Cell , vol.157 , pp. 624-635
    • Li, G.W.1    Burkhardt, D.2    Gross, C.3    Weissman, J.S.4
  • 154
    • 0028802746 scopus 로고
    • A hierarchy of ATP-consuming processes in mammalian cells
    • Buttgereit FM, Brand D, (1995). A hierarchy of ATP-consuming processes in mammalian cells. Biochem J 312: 163-167.
    • (1995) Biochem J , vol.312 , pp. 163-167
    • Buttgereit, F.M.1    Brand, D.2
  • 155
    • 0029963423 scopus 로고    scopus 로고
    • Sequence requirements for membrane assembly of polytopic membrane proteins: Molecular dissection of the membrane insertion process and topogenesis of the human mdr3 P-glycoprotein
    • Zhang JT, (1996). Sequence requirements for membrane assembly of polytopic membrane proteins: molecular dissection of the membrane insertion process and topogenesis of the human mdr3 P-glycoprotein. Mol Biol Cell 7: 1709-1721.
    • (1996) Mol Biol Cell , vol.7 , pp. 1709-1721
    • Zhang, J.T.1
  • 156
    • 35748932922 scopus 로고    scopus 로고
    • Topology inversion of SecG is essential for cytosolic SecA-dependent stimulation of protein translocation
    • Sugai R, Takemae K, Tokuda H, Nishiyama K, (2007). Topology inversion of SecG is essential for cytosolic SecA-dependent stimulation of protein translocation. J Biol Chem 282: 29540-29548.
    • (2007) J Biol Chem , vol.282 , pp. 29540-29548
    • Sugai, R.1    Takemae, K.2    Tokuda, H.3    Nishiyama, K.4
  • 157
    • 84904179187 scopus 로고    scopus 로고
    • Folding of aquaporin 1: Multiple evidence that helix 3 can shift out of the membrane core
    • Virkki MT, Agrawal N, Edsbacker E, Cristobal S, Elofsson A, Kauko A, (2014). Folding of aquaporin 1: multiple evidence that helix 3 can shift out of the membrane core. Protein Sci 23: 981-992.
    • (2014) Protein Sci , vol.23 , pp. 981-992
    • Virkki, M.T.1    Agrawal, N.2    Edsbacker, E.3    Cristobal, S.4    Elofsson, A.5    Kauko, A.6
  • 158
    • 79955650131 scopus 로고    scopus 로고
    • A look at arginine in membranes
    • Hristova K, Wimley WC, (2011). A look at arginine in membranes. J Membr Biol 239: 49-56.
    • (2011) J Membr Biol , vol.239 , pp. 49-56
    • Hristova, K.1    Wimley, W.C.2
  • 159
    • 34247633528 scopus 로고    scopus 로고
    • On the thermodynamic stability of a charged arginine side chain in a transmembrane helix
    • Dorairaj S, Allen TW, (2007). On the thermodynamic stability of a charged arginine side chain in a transmembrane helix. Proc Natl Acad Sci USA 104: 4943-4948.
    • (2007) Proc Natl Acad Sci USA , vol.104 , pp. 4943-4948
    • Dorairaj, S.1    Allen, T.W.2
  • 161
    • 20044389842 scopus 로고    scopus 로고
    • Membrane insertion of a potassium-channel voltage sensor
    • Hessa T, White SH, von Heijne G, (2005). Membrane insertion of a potassium-channel voltage sensor. Science 307: 1427.
    • (2005) Science , vol.307 , pp. 1427
    • Hessa, T.1    White, S.H.2    Von Heijne, G.3
  • 162
    • 79954723199 scopus 로고    scopus 로고
    • On the role of anionic lipids in charged protein interactions with membranes
    • Vorobyov I, Allen TW, (2011). On the role of anionic lipids in charged protein interactions with membranes. Biochim Biophys Acta 1808: 1673-1683.
    • (2011) Biochim Biophys Acta , vol.1808 , pp. 1673-1683
    • Vorobyov, I.1    Allen, T.W.2
  • 163
    • 0026501551 scopus 로고
    • Functions of signal and signal-anchor sequences are determined by the balance between the hydrophobic segment and the N-terminal charge
    • Sakaguchi M, Tomiyoshi R, Kuroiwa T, Mihara K, Omura T, (1992). Functions of signal and signal-anchor sequences are determined by the balance between the hydrophobic segment and the N-terminal charge. Proc Natl Acad Sci USA 89: 16-19.
    • (1992) Proc Natl Acad Sci USA , vol.89 , pp. 16-19
    • Sakaguchi, M.1    Tomiyoshi, R.2    Kuroiwa, T.3    Mihara, K.4    Omura, T.5
  • 164
    • 77953625243 scopus 로고    scopus 로고
    • MPRAP: An accessibility predictor for a-helical transmembrane proteins that performs well inside and outside the membrane
    • Illergard K, Callegari S, Elofsson A, (2010). MPRAP: an accessibility predictor for a-helical transmembrane proteins that performs well inside and outside the membrane. BMC Bioinform 11: 333.
    • (2010) BMC Bioinform , vol.11 , pp. 333
    • Illergard, K.1    Callegari, S.2    Elofsson, A.3
  • 165
    • 0037180396 scopus 로고    scopus 로고
    • The tenth membrane region of band 3 is initially exposed to the luminal side of the endoplasmic reticulum and then integrated into a partially folded band 3 intermediate
    • Kanki T, Sakaguchi M, Kitamura A, Sato T, Mihara K, Hamasaki N, (2002). The tenth membrane region of band 3 is initially exposed to the luminal side of the endoplasmic reticulum and then integrated into a partially folded band 3 intermediate. Biochemistry 41: 13973-13981.
    • (2002) Biochemistry , vol.41 , pp. 13973-13981
    • Kanki, T.1    Sakaguchi, M.2    Kitamura, A.3    Sato, T.4    Mihara, K.5    Hamasaki, N.6
  • 166
    • 4744344168 scopus 로고    scopus 로고
    • Topogenesis of nhe1: Direct insertion of the membrane loop and sequestration of cryptic glycosylation and processing sites just after tm9
    • Sato Y, Ariyoshi N, Mihara K, Sakaguchi M, (2004). Topogenesis of nhe1: direct insertion of the membrane loop and sequestration of cryptic glycosylation and processing sites just after tm9. Biochem Biophys Res Commun 324: 281-287.
    • (2004) Biochem Biophys Res Commun , vol.324 , pp. 281-287
    • Sato, Y.1    Ariyoshi, N.2    Mihara, K.3    Sakaguchi, M.4
  • 167
    • 84872016140 scopus 로고    scopus 로고
    • A gating motif in the translocation channel sets the hydrophobicity threshold for signal sequence function
    • Trueman SF, Mandon EC, Gilmore R, (2012). A gating motif in the translocation channel sets the hydrophobicity threshold for signal sequence function. J Cell Biol 199: 907-918.
    • (2012) J Cell Biol , vol.199 , pp. 907-918
    • Trueman, S.F.1    Mandon, E.C.2    Gilmore, R.3
  • 168
    • 77952378779 scopus 로고    scopus 로고
    • The hydrophobic core of the sec61 translocon defines the hydrophobicity threshold for membrane integration
    • Junne T, Kocik L, Spiess M, (2010). The hydrophobic core of the sec61 translocon defines the hydrophobicity threshold for membrane integration. Mol Biol Cell 21: 1662-1670.
    • (2010) Mol Biol Cell , vol.21 , pp. 1662-1670
    • Junne, T.1    Kocik, L.2    Spiess, M.3
  • 169
    • 84901715964 scopus 로고    scopus 로고
    • Structural and functional profiling of the lateral gate of the sec61 translocon
    • Reithinger JH, Yim C, Kim S, Lee H, Kim H, (2014). Structural and functional profiling of the lateral gate of the sec61 translocon. J Biol Chem 289: 15845-15855.
    • (2014) J Biol Chem , vol.289 , pp. 15845-15855
    • Reithinger, J.H.1    Yim, C.2    Kim, S.3    Lee, H.4    Kim, H.5
  • 170
    • 0030611388 scopus 로고    scopus 로고
    • The aqueous pore through the translocon has a diameter of 40-60 a during cotranslational protein translocation at the ER membrane
    • Hamman BD, Chen JC, Johnson EE, Johnson AE, (1997). The aqueous pore through the translocon has a diameter of 40-60 a during cotranslational protein translocation at the ER membrane. Cell 89: 535-544.
    • (1997) Cell , vol.89 , pp. 535-544
    • Hamman, B.D.1    Chen, J.C.2    Johnson, E.E.3    Johnson, A.E.4
  • 172
    • 54049111011 scopus 로고    scopus 로고
    • Structure of a complex of the ATPase SecA and the protein-translocation channel
    • Zimmer J, Nam Y, Rapoport TA, (2008). Structure of a complex of the ATPase SecA and the protein-translocation channel. Nature 455: 936-943.
    • (2008) Nature , vol.455 , pp. 936-943
    • Zimmer, J.1    Nam, Y.2    Rapoport, T.A.3
  • 173
    • 42449130051 scopus 로고    scopus 로고
    • Specific transmembrane segments are selectively delayed at the ER translocon during opsin biogenesis
    • Ismail N, Crawshaw SG, Cross BC, Haagsma AC, High S, (2008). Specific transmembrane segments are selectively delayed at the ER translocon during opsin biogenesis. Biochem J 411: 495-506.
    • (2008) Biochem J , vol.411 , pp. 495-506
    • Ismail, N.1    Crawshaw, S.G.2    Cross, B.C.3    Haagsma, A.C.4    High, S.5
  • 175
    • 84890856922 scopus 로고    scopus 로고
    • Transmembrane segments form tertiary hairpins in the folding vestibule of the ribosome
    • Tu L, Khanna P, Deutsch C, (2014). Transmembrane segments form tertiary hairpins in the folding vestibule of the ribosome. J Mol Biol 426: 185-198.
    • (2014) J Mol Biol , vol.426 , pp. 185-198
    • Tu, L.1    Khanna, P.2    Deutsch, C.3
  • 176
    • 38049058405 scopus 로고    scopus 로고
    • Two translocating hydrophilic segments of a nascent chain span the ER membrane during multispanning protein topogenesis
    • Kida Y, Morimoto F, Sakaguchi M, (2007). Two translocating hydrophilic segments of a nascent chain span the ER membrane during multispanning protein topogenesis. J Cell Biol 179: 1441-1452.
    • (2007) J Cell Biol , vol.179 , pp. 1441-1452
    • Kida, Y.1    Morimoto, F.2    Sakaguchi, M.3
  • 177
    • 61949084073 scopus 로고    scopus 로고
    • Sequence-specific retention and regulated integration of a nascent membrane protein by the endoplasmic reticulum sec61 translocon
    • Pitonzo D, Yang Z, Matsumura Y, Johnson AE, Skach WR, (2009). Sequence-specific retention and regulated integration of a nascent membrane protein by the endoplasmic reticulum sec61 translocon. Mol Biol Cell 20: 685-698.
    • (2009) Mol Biol Cell , vol.20 , pp. 685-698
    • Pitonzo, D.1    Yang, Z.2    Matsumura, Y.3    Johnson, A.E.4    Skach, W.R.5
  • 178
    • 33646191829 scopus 로고    scopus 로고
    • Size, motion, and function of the SecY translocon revealed by molecular dynamics simulations with virtual probes
    • Tian P, Andricioaei I, (2006). Size, motion, and function of the SecY translocon revealed by molecular dynamics simulations with virtual probes. Biophys J 90: 2718-2730.
    • (2006) Biophys J , vol.90 , pp. 2718-2730
    • Tian, P.1    Andricioaei, I.2
  • 179
    • 85017732895 scopus 로고    scopus 로고
    • Mechanisms of integral membrane protein insertion and folding
    • Cymer F, von Heijne GS, White H., Mechanisms of integral membrane protein insertion and folding. J Mol Biol.
    • J Mol Biol
    • Cymer, F.1    Von Heijne, G.S.2    White, H.3
  • 180
    • 0024448087 scopus 로고
    • Lipid traffic in animal cells
    • van Meer G, (1989). Lipid traffic in animal cells. Annu Rev Cell Biol 5: 247-275.
    • (1989) Annu Rev Cell Biol , vol.5 , pp. 247-275
    • Van Meer, G.1


* 이 정보는 Elsevier사의 SCOPUS DB에서 KISTI가 분석하여 추출한 것입니다.