Cholesterol increases kinetic, energetic,and mechanical stability of the human β2-adrenergic receptor

Proceedings of the National Academy of Sciences of the United States of America

Volumn 109, Issue 50, 2012, Pages

  Zocher, Michael ^a   Zhang, Cheng ^b   Rasmussen, Søren G F ^b   Kobilka, Brian K ^b   Müller, Daniel J ^a  

^a ETH ZURICH   (Switzerland)

^b STANFORD UNIVERSITY SCHOOL OF MEDICINE   (United States)

Author keywords

Atomic force microscopy; Energy landscape; Intermolecular and intramolecular interactions; Proteoliposomes

Indexed keywords

BETA 2 ADRENERGIC RECEPTOR; CHOLESTEROL HYDROGEN SUCCINATE; G PROTEIN COUPLED RECEPTOR;

ARTICLE; ATOMIC FORCE MICROSCOPY; BINDING SITE; HUMAN; IN VITRO STUDY; KINETICS; LIGAND BINDING; LIPID MEMBRANE; MECHANICAL TORSION; MOLECULAR INTERACTION; PRIORITY JOURNAL; PROTEIN CONFORMATION; PROTEIN STABILITY; PROTEIN UNFOLDING;

ANIMALS; BIOMECHANICS; CHOLESTEROL ESTERS; ENERGY METABOLISM; HUMANS; KINETICS; MICROSCOPY, ATOMIC FORCE; MODELS, MOLECULAR; PROTEIN CONFORMATION; PROTEIN INTERACTION MAPPING; PROTEIN STABILITY; PROTEOLIPIDS; RECEPTORS, ADRENERGIC, BETA-2; RECOMBINANT PROTEINS; SF9 CELLS; SPODOPTERA; UNFOLDED PROTEIN RESPONSE;

EUKARYOTA;

EID: 84870896671     PISSN: 00278424     EISSN: 10916490     Source Type: Journal    
DOI: 10.1073/pnas.1210373109     Document Type: Article

References (84)

1. Milligan G, Svoboda P, Brown CM (1994) Why are there so many adrenoceptor subtypes? Biochem Pharmacol 48(6):1059-1071. (Pubitemid 24298355)
2. Takeda S, Kadowaki S, Haga T, Takaesu H, Mitaku S (2002) Identification of G protein-coupled receptor genes from the human genome sequence. FEBS Lett 520(1-3):97-101. (Pubitemid 34607281)
3. Bai TR (1992) Beta 2 adrenergic receptors in asthma: A current perspective. Lung 170 (3):125-141.
4. Barnes PJ (1993) Beta-adrenoceptors on smooth muscle, nerves and inflammatory cells. Life Sci 52(26):2101-2109.
5. Smiley RM, Finster M (1996) Do receptors get pregnant too? Adrenergic receptor alterations in human pregnancy. J Matern Fetal Med 5(3):106-114.
6. Overington JP, Al-Lazikani B, Hopkins AL (2006) How many drug targets are there? Nat Rev Drug Discov 5(12):993-996. (Pubitemid 44835126)
7. Wishart DS, et al. (2006) DrugBank: A comprehensive resource for in silico drug discovery and exploration. Nucleic Acids Res 34(Database issue):D668-D672.
8. Rasmussen SG, et al. (2007) Crystal structure of the human beta2 adrenergic G-protein-coupled receptor. Nature 450(7168):383-387. (Pubitemid 350126755)
9. Cherezov V, et al. (2007) High-resolution crystal structure of an engineered human beta2-adrenergic G protein-coupled receptor. Science 318(5854):1258-1265. (Pubitemid 350172884)
10. Rosenbaum DM, et al. (2007) GPCR engineering yields high-resolution structural insights into beta2-adrenergic receptor function. Science 318(5854):1266-1273. (Pubitemid 350172885)
11. Rasmussen SG, et al. (2011) Structure of a nanobody-stabilized active state of the β(2) adrenoceptor. Nature 469(7329):175-180.
12. Rosenbaum DM, et al. (2011) Structure and function of an irreversible agonist-β(2) adrenoceptor complex. Nature 469(7329):236-240.
13. Watts A, Volotovski ID, Marsh D (1979) Rhodopsin-lipid associations in bovine rod outer segment membranes. Identification of immobilized lipid by spin-labels. Biochemistry 18(22):5006-5013. (Pubitemid 10204654)
14. Fretten P, Morris SJ, Watts A, Marsh D (1980) Lipid-lipid and lipid-protein interactions in chromaffin granule membranes. A spin label ESR study. Biochim Biophys Acta 598 (2):247-259.
15. Marsh D, et al. (1982) ESR spin-label studies of lipid-protein interactions in membranes. Biophys J 37(1):265-274.
16. Engelman DM (2005) Membranes are more mosaic than fluid. Nature 438(7068):578-580.
17. Phillips R, Ursell T, Wiggins P, Sens P (2009) Emerging roles for lipids in shaping membrane-protein function. Nature 459(7245):379-385.
18. Simons K, Gerl MJ (2010) Revitalizing membrane rafts: New tools and insights. Nat Rev Mol Cell Biol 11(10):688-699.
19. Lingwood D, Simons K (2010) Lipid rafts as a membrane-organizing principle. Science 327(5961):46-50.
20. Oates J, Watts A (2011) Uncovering the intimate relationship between lipids, cholesterol and GPCR activation. Curr Opin Struct Biol 21(6):802-807.
21. Lee AG (2004) How lipids affect the activities of integral membrane proteins. Biochim Biophys Acta 1666(1-2):62-87.
22. Gimpl G, Burger K, Fahrenholz F (1997) Cholesterol as modulator of receptor function. Biochemistry 36(36):10959-10974. (Pubitemid 27396253)
23. Pang L, Graziano M, Wang S (1999) Membrane cholesterol modulates galanin-GalR2 interaction. Biochemistry 38(37):12003-12011.
24. Burger K, Gimpl G, Fahrenholz F (2000) Regulation of receptor function by cholesterol. Cell Mol Life Sci 57(11):1577-1592.
25. Pucadyil TJ, Chattopadhyay A (2004) Cholesterol modulates ligand binding and G-protein coupling to serotonin(1A) receptors from bovine hippocampus. Biochim Biophys Acta 1663(1-2):188-200. (Pubitemid 38625593)
26. Pucadyil TJ, Chattopadhyay A (2006) Role of cholesterol in the function and organization of G-protein coupled receptors. Prog Lipid Res 45(4):295-333. (Pubitemid 43818130)
27. Rajendran L, Knölker HJ, Simons K (2010) Subcellular targeting strategies for drug design and delivery. Nat Rev Drug Discov 9(1):29-42.
28. Xiang Y, Rybin VO, Steinberg SF, Kobilka B (2002) Caveolar localization dictates physiologic signaling of beta 2-adrenoceptors in neonatal cardiac myocytes. J Biol Chem 277(37):34280-34286.
29. Yao Z, Kobilka B (2005) Using synthetic lipids to stabilize purified beta2 adrenoceptor in detergent micelles. Anal Biochem 343(2):344-346. (Pubitemid 41074051)
30. Hanson MA, et al. (2008) A specific cholesterol binding site is established by the 2.8 A structure of the human beta2-adrenergic receptor. Structure 16(6):897-905. (Pubitemid 351778384)
31. Kedrov A, Janovjak H, Sapra KT, Müller DJ (2007) Deciphering molecular interactions of native membrane proteins by single-molecule force spectroscopy. Annu Rev Biophys Biomol Struct 36:233-260. (Pubitemid 46998118)
32. Engel A, Gaub HE (2008) Structure and mechanics of membrane proteins. Annu Rev Biochem 77:127-148.
33. Janovjak H, Sapra KT, Kedrov A, Müller DJ (2008) From valleys to ridges: Exploring the dynamic energy landscape of single membrane proteins. ChemPhysChem 9(7):954-966.
34. Park PS, et al. (2007) Stabilizing effect of Zn2+ in native bovine rhodopsin. J Biol Chem 282(15):11377-11385. (Pubitemid 47100760)
35. Kedrov A, Appel M, Baumann H, Ziegler C, Muller DJ (2008) Examining the dynamic energy landscape of an antiporter upon inhibitor binding. J Mol Biol 375(5):1258-1266.
36. Bippes CA, et al. (2009) Substrate binding tunes conformational flexibility and kinetic stability of an amino acid antiporter. J Biol Chem 284(28):18651-18663.
37. Kedrov A, et al. (2010) Probing the interactions of carboxy-atractyloside and atractyloside with the yeast mitochondrial ADP/ATP carrier. Structure 18(1):39-46.
38. Damaghi M, et al. (2010) Dual energy landscape: The functional state of the β-barrel outer membrane protein G molds its unfolding energy landscape. Proteomics 10(23):4151-4162.
39. Ge L, Perez C, Waclawska I, Ziegler C, Muller DJ (2011) Locating an extracellular K+-dependent interaction site that modulates betaine-binding of the Na+-coupled betaine symporter BetP. Proc Natl Acad Sci USA 108(43):E890-E898.
40. Fung JJ, et al. (2009) Ligand-regulated oligomerization of beta(2)-adrenoceptors in a model lipid bilayer. EMBO J 28(21):3315-3328.
41. Oates J, et al. (2012) The role of cholesterol on the activity and stability of neurotensin receptor 1. Biochim Biophys Acta 1818(9):2228-2233.
42. Gimpl G, Fahrenholz F (2002) Cholesterol as stabilizer of the oxytocin receptor. Biochim Biophys Acta 1564(2):384-392.
43. Chae PS, et al. (2010) Maltose-neopentyl glycol (MNG) amphiphiles for solubilization, stabilization and crystallization of membrane proteins. Nat Methods 7(12):1003-1008.
44. Saxena R, Chattopadhyay A (2012) Membrane cholesterol stabilizes the human serotonin(1A) receptor. Biochim Biophys Acta 1818(12):2936-2942.
45. Evans E (2001) Probing the relation between force - lifetime - and chemistry in single molecular bonds. Annu Rev Biophys Biomol Struct 30:105-128.
46. Evans E, Ritchie K (1997) Dynamic strength of molecular adhesion bonds. Biophys J 72 (4):1541-1555. (Pubitemid 27133095)
47. Evans E (1998) Energy landscapes of biomolecular adhesion and receptor anchoring at interfaces explored with dynamic force spectroscopy. Faraday Discuss 111(111):1-16.
48. Janovjak H, et al. (2004) Probing the energy landscape of the membrane protein bacteriorhodopsin. Structure 12(5):871-879. (Pubitemid 38595775)
49. Sapra KT, Balasubramanian GP, Labudde D, Bowie JU, Muller DJ (2008) Point mutations in membrane proteins reshape energy landscape and populate different unfolding pathways. J Mol Biol 376(4):1076-1090.
50. Sapra KT, Doehner J, Renugopalakrishnan V, Padrós E, Muller DJ (2008) Role of extracellular glutamic acids in the stability and energy landscape of bacteriorhodopsin. Biophys J 95(7):3407-3418.
51. Kawamura S, Colozo AT,Müller DJ, Park PS (2010) Conservation of molecular interactions stabilizing bovine and mouse rhodopsin. Biochemistry 49(49):10412-10420.
52. Wells JW (1992) Analysis and interpretation of binding at equilibrium. Receptor-Ligand Interactions: A Practical Approach, ed Hulme EC (Oxford Univ Press, Oxford).
53. Motulsky HJ, Christopoulos A (2004) Fitting Models to Biological Data Using Linear and Nonlinear Regression: A Practical Guide to Curve Fitting (Oxford Univ Press, New York).
54. Janovjak H, Kessler M, Oesterhelt D, Gaub H, Müller DJ (2003) Unfolding pathways of native bacteriorhodopsin depend on temperature. EMBO J 22(19):5220-5229. (Pubitemid 37222041)
55. Kumar S, Ma B, Tsai CJ, Sinha N, Nussinov R (2000) Folding and binding cascades: Dynamic landscapes and population shifts. Protein Sci 9(1):10-19. (Pubitemid 30070934)
56. Oliveberg M, Wolynes PG (2005) The experimental survey of protein-folding energy landscapes. Q Rev Biophys 38(3):245-288. (Pubitemid 44268537)
57. Dietz H, Berkemeier F, Bertz M, Rief M (2006) Anisotropic deformation response of single protein molecules. Proc Natl Acad Sci USA 103(34):12724-12728. (Pubitemid 44298628)
58. Evans E, Needham D (1986) Giant vesicle bilayers composed of mixtures of lipids, cholesterol and polypeptides. Thermomechanical and (mutual) adherence properties. Faraday Discuss Chem Soc 81:267-280.
59. Needham D, Nunn RS (1990) Elastic deformation and failure of lipid bilayer membranes containing cholesterol. Biophys J 58(4):997-1009. (Pubitemid 20307868)
60. Dudko OK, Hummer G, Szabo A (2008) Theory, analysis, and interpretation of single-molecule force spectroscopy experiments. Proc Natl Acad Sci USA 105(41):15755-15760.
61. Hebert TE, et al. (1996) A peptide derived from a beta2-adrenergic receptor transmembrane domain inhibits both receptor dimerization and activation. J Biol Chem 271(27):16384-16392. (Pubitemid 26236264)
62. Terrillon S, Bouvier M (2004) Roles of G-protein-coupled receptor dimerization. EMBO Rep 5(1):30-34. (Pubitemid 38228524)
63. Milligan G (2004) G protein-coupled receptor dimerization: Function and ligand pharmacology. Mol Pharmacol 66(1):1-7.
64. Liang Y, et al. (2003) Organization of the G protein-coupled receptors rhodopsin and opsin in native membranes. J Biol Chem 278(24):21655-21662. (Pubitemid 36792566)
65. Guo W, et al. (2008) Dopamine D2 receptors form higher order oligomers at physiological expression levels. EMBO J 27(17):2293-2304.
66. Zocher M, Fung JJ, Kobilka BK, Müller DJ (2012) Ligand-specific interactions modulate kinetic, energetic, and mechanical properties of the human β2 adrenergic receptor. Structure 20(8):1391-1402.
67. Kirilovsky J, Schramm M (1983) Delipidation of a beta-adrenergic receptor preparation and reconstitution by specific lipids. J Biol Chem 258(11):6841-6849. (Pubitemid 13059944)
68. Kobilka BK, et al. (1988) Chimeric alpha 2-,beta 2-adrenergic receptors: Delineation of domains involved in effector coupling and ligand binding specificity. Science 240 (4857):1310-1316.
69. Gether U, Kobilka BK (1998) G protein-coupled receptors. II. Mechanism of agonist activation. J Biol Chem 273(29):17979-17982.
70. Ben-Arie N, Gileadi C, Schramm M (1988) Interaction of the beta-adrenergic receptor with Gs following delipidation. Specific lipid requirements for Gs activation and GTPase function. Eur J Biochem 176(3):649-654.
71. Reiter E, Lefkowitz RJ (2006) GRKs and beta-arrestins: Roles in receptor silencing, trafficking and signaling. Trends Endocrinol Metab 17(4):159-165.
72. Xiang Y, Kobilka B (2003) The PDZ-binding motif of the beta2-adrenoceptor is essential for physiologic signaling and trafficking in cardiac myocytes. Proc Natl Acad Sci USA 100(19):10776-10781. (Pubitemid 37140104)
73. Kobilka BK, Deupi X (2007) Conformational complexity of G-protein-coupled receptors. Trends Pharmacol Sci 28(8):397-406. (Pubitemid 47087966)
74. Struckmeier J, et al. (2008) Fully automated single-molecule force spectroscopy for screening applications. Nanotechnology 19(38):384020.
75. Butt HJ, Jaschke M (1995) Calculation of thermal noise in atomic-force microscopy. Nanotechnology 6:1-7.
76. Florin EL, et al. (1995) Sensing specific molecular-interactions with the atomic-force microscope. Biosens Bioelectron 10:895-901.
77. Müller DJ, Engel A (2007) Atomic force microscopy and spectroscopy of native membrane proteins. Nat Protoc 2(9):2191-2197. (Pubitemid 351565857)
78. Muller DJ (2008) AFM: A nanotool in membrane biology. Biochemistry 47(31):7986-7998.
79. Müller DJ, et al. (2002) Stability of bacteriorhodopsin alpha-helices and loops analyzed by single-molecule force spectroscopy. Biophys J 83(6):3578-3588. (Pubitemid 36041975)
80. Bustamante C, Marko JF, Siggia ED, Smith S (1994) Entropic elasticity of lambda-phage DNA. Science 265(5178):1599-1600.
81. Rief M, Gautel M, Oesterhelt F, Fernandez JM, Gaub HE (1997) Reversible unfolding of individual titin immunoglobulin domains by AFM. Science 276(5315):1109-1112. (Pubitemid 27218118)
82. Krieger F, Fierz B, Bieri O, Drewello M, Kiefhaber T (2003) Dynamics of unfolded polypeptide chains as model for the earliest steps in protein folding. J Mol Biol 332(1):265-274. (Pubitemid 36999746)
83. Dietz H, Rief M (2004) Exploring the energy landscape of GFP by single-molecule mechanical experiments. Proc Natl Acad Sci USA 101(46):16192-16197. (Pubitemid 39552821)
84. Gräter F, Grubmüller H (2007) Fluctuations of primary ubiquitin folding intermediates in a force clamp. J Struct Biol 157(3):557-569.