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Volumn 387, Issue 2, 2009, Pages 348-362

Revealing a Concealed Intermediate that Forms after the Rate-limiting Step of Refolding of the SH3 Domain of PI3 Kinase

Author keywords

burst phase; intermediates; interrupted unfolding; SH3 domain; transition state

Indexed keywords

PHOSPHATIDYLINOSITOL 3 KINASE;

EID: 61649112900     PISSN: 00222836     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.jmb.2009.01.060     Document Type: Article
Times cited : (24)

References (55)
  • 1
    • 0026345750 scopus 로고
    • Folding of chymotrypsin inhibitor 2. 1. Evidence for a two-state transition
    • Jackson S.E., and Fersht A.R. Folding of chymotrypsin inhibitor 2. 1. Evidence for a two-state transition. Biochemistry 30 (1991) 10428-10435
    • (1991) Biochemistry , vol.30 , pp. 10428-10435
    • Jackson, S.E.1    Fersht, A.R.2
  • 2
    • 0028856785 scopus 로고
    • Optimization of rates of protein folding: the nucleation-condensation mechanism and its implications
    • Fersht A.R. Optimization of rates of protein folding: the nucleation-condensation mechanism and its implications. Proc. Natl Acad. Sci. USA 92 (1995) 10869-11087
    • (1995) Proc. Natl Acad. Sci. USA , vol.92 , pp. 10869-11087
    • Fersht, A.R.1
  • 3
    • 0038581260 scopus 로고    scopus 로고
    • Hidden intermediates and the Levinthal paradox in the folding of small proteins
    • Bai Y. Hidden intermediates and the Levinthal paradox in the folding of small proteins. Biochem. Biophys. Res. Commun. 305 (2003) 785-788
    • (2003) Biochem. Biophys. Res. Commun. , vol.305 , pp. 785-788
    • Bai, Y.1
  • 5
    • 0030057477 scopus 로고    scopus 로고
    • Evidence for a three-state model of protein folding from kinetic analysis of ubiquitin variants with altered core residues
    • Khorasanizadeh S., Peters I.D., and Roder H. Evidence for a three-state model of protein folding from kinetic analysis of ubiquitin variants with altered core residues. Nat. Struct. Biol. 3 (1996) 193-205
    • (1996) Nat. Struct. Biol. , vol.3 , pp. 193-205
    • Khorasanizadeh, S.1    Peters, I.D.2    Roder, H.3
  • 6
    • 0037192121 scopus 로고    scopus 로고
    • pH and urea dependence of amide hydrogen-deuterium exchange rates in the beta-trefoil protein hisactophilin
    • Houliston R.S., Liu C., Singh L.M., and Meiering E.M. pH and urea dependence of amide hydrogen-deuterium exchange rates in the beta-trefoil protein hisactophilin. Biochemistry 41 (2002) 1182-1194
    • (2002) Biochemistry , vol.41 , pp. 1182-1194
    • Houliston, R.S.1    Liu, C.2    Singh, L.M.3    Meiering, E.M.4
  • 7
    • 0035965128 scopus 로고    scopus 로고
    • Acidic conditions stabilise intermediates populated during the folding of Im7 and Im9
    • Gorski S.A., Capaldi A.P., Kleanthous C., and Radford S.E. Acidic conditions stabilise intermediates populated during the folding of Im7 and Im9. J. Mol. Biol. 312 (2001) 849-863
    • (2001) J. Mol. Biol. , vol.312 , pp. 849-863
    • Gorski, S.A.1    Capaldi, A.P.2    Kleanthous, C.3    Radford, S.E.4
  • 9
    • 33748774168 scopus 로고    scopus 로고
    • HX-ESI-MS and optical studies of the unfolding of thioredoxin indicate stabilization of a partially unfolded, aggregation-competent intermediate at low pH
    • Wani A.H., and Udgaonkar J.B. HX-ESI-MS and optical studies of the unfolding of thioredoxin indicate stabilization of a partially unfolded, aggregation-competent intermediate at low pH. Biochemistry 45 (2006) 11226-11238
    • (2006) Biochemistry , vol.45 , pp. 11226-11238
    • Wani, A.H.1    Udgaonkar, J.B.2
  • 11
    • 0029868589 scopus 로고    scopus 로고
    • Nonlinear free energy relationships in Arc repressor unfolding imply the existence of unstable, native-like folding intermediates
    • Jonsson T., Waldburger C.D., and Sauer R.T. Nonlinear free energy relationships in Arc repressor unfolding imply the existence of unstable, native-like folding intermediates. Biochemistry 35 (1996) 4795-4802
    • (1996) Biochemistry , vol.35 , pp. 4795-4802
    • Jonsson, T.1    Waldburger, C.D.2    Sauer, R.T.3
  • 12
    • 0030787174 scopus 로고    scopus 로고
    • Multiple intermediates and transition states during protein unfolding
    • Zaidi F.N., Nath U., and Udgaonkar J.B. Multiple intermediates and transition states during protein unfolding. Nat. Struct. Biol. 4 (1997) 1016-1024
    • (1997) Nat. Struct. Biol. , vol.4 , pp. 1016-1024
    • Zaidi, F.N.1    Nath, U.2    Udgaonkar, J.B.3
  • 13
    • 0037176861 scopus 로고    scopus 로고
    • Characterization of the unfolding of ribonuclease a by a pulsed hydrogen exchange study: evidence for competing pathways for unfolding
    • Juneja J., and Udgaonkar J.B. Characterization of the unfolding of ribonuclease a by a pulsed hydrogen exchange study: evidence for competing pathways for unfolding. Biochemistry 41 (2002) 2641-2654
    • (2002) Biochemistry , vol.41 , pp. 2641-2654
    • Juneja, J.1    Udgaonkar, J.B.2
  • 14
    • 0037225280 scopus 로고    scopus 로고
    • Evidence for sequential barriers and obligatory intermediates in apparent two-state protein folding
    • Sanchez I.E., and Kiefhaber T. Evidence for sequential barriers and obligatory intermediates in apparent two-state protein folding. J. Mol. Biol. 325 (2003) 367-376
    • (2003) J. Mol. Biol. , vol.325 , pp. 367-376
    • Sanchez, I.E.1    Kiefhaber, T.2
  • 15
    • 0037022179 scopus 로고    scopus 로고
    • Unfolding rates of barstar determined in native and low denaturant conditions indicate the presence of intermediates
    • Sridevi K., and Udgaonkar J.B. Unfolding rates of barstar determined in native and low denaturant conditions indicate the presence of intermediates. Biochemistry 41 (2002) 1568-1578
    • (2002) Biochemistry , vol.41 , pp. 1568-1578
    • Sridevi, K.1    Udgaonkar, J.B.2
  • 16
    • 48249140760 scopus 로고    scopus 로고
    • Multiple routes and structural heterogeneity in protein folding
    • Udgaonkar J.B. Multiple routes and structural heterogeneity in protein folding. Annu. Rev. Biophys. 37 (2008) 489-510
    • (2008) Annu. Rev. Biophys. , vol.37 , pp. 489-510
    • Udgaonkar, J.B.1
  • 17
    • 0029643523 scopus 로고
    • Protein folding intermediates: native-state hydrogen exchange
    • Bai Y., Sosnick T.R., Mayne L., and Englander S.W. Protein folding intermediates: native-state hydrogen exchange. Science 269 (1995) 192-197
    • (1995) Science , vol.269 , pp. 192-197
    • Bai, Y.1    Sosnick, T.R.2    Mayne, L.3    Englander, S.W.4
  • 18
    • 34247639886 scopus 로고    scopus 로고
    • Exploring subdomain cooperativity in T4 lysozyme II: uncovering the C-terminal subdomain as a hidden intermediate in the kinetic folding pathway
    • Cellitti J., Bernstein R., and Marqusee S. Exploring subdomain cooperativity in T4 lysozyme II: uncovering the C-terminal subdomain as a hidden intermediate in the kinetic folding pathway. Protein Sci. 16 (2007) 852-862
    • (2007) Protein Sci. , vol.16 , pp. 852-862
    • Cellitti, J.1    Bernstein, R.2    Marqusee, S.3
  • 19
    • 0035909818 scopus 로고    scopus 로고
    • pH-jump-induced folding and unfolding studies of barstar: evidence for multiple folding and unfolding pathways
    • Rami B.R., and Udgaonkar J.B. pH-jump-induced folding and unfolding studies of barstar: evidence for multiple folding and unfolding pathways. Biochemistry 40 (2001) 15267-15279
    • (2001) Biochemistry , vol.40 , pp. 15267-15279
    • Rami, B.R.1    Udgaonkar, J.B.2
  • 20
    • 0037414459 scopus 로고    scopus 로고
    • Real-time NMR kinetic studies provide global and residue-specific information on the non-cooperative unfolding of the beta-trefoil protein, interleukin-1beta
    • Roy M., and Jennings P.A. Real-time NMR kinetic studies provide global and residue-specific information on the non-cooperative unfolding of the beta-trefoil protein, interleukin-1beta. J. Mol. Biol. 328 (2003) 693-703
    • (2003) J. Mol. Biol. , vol.328 , pp. 693-703
    • Roy, M.1    Jennings, P.A.2
  • 21
    • 35448932093 scopus 로고    scopus 로고
    • Characterization of the folding and unfolding reactions of single-chain monellin: evidence for multiple intermediates and competing pathways
    • Patra A.K., and Udgaonkar J.B. Characterization of the folding and unfolding reactions of single-chain monellin: evidence for multiple intermediates and competing pathways. Biochemistry 46 (2007) 11727-11743
    • (2007) Biochemistry , vol.46 , pp. 11727-11743
    • Patra, A.K.1    Udgaonkar, J.B.2
  • 22
    • 33847769109 scopus 로고    scopus 로고
    • Mechanism of formation of amyloid protofibrils of barstar from soluble oligomers: evidence for multiple steps and lateral association coupled to conformational conversion
    • Kumar S., Mohanty S.K., and Udgaonkar J.B. Mechanism of formation of amyloid protofibrils of barstar from soluble oligomers: evidence for multiple steps and lateral association coupled to conformational conversion. J. Mol. Biol. 367 (2007) 1186-1204
    • (2007) J. Mol. Biol. , vol.367 , pp. 1186-1204
    • Kumar, S.1    Mohanty, S.K.2    Udgaonkar, J.B.3
  • 23
    • 0031815749 scopus 로고    scopus 로고
    • How do small single-domain proteins fold?
    • Jackson S.E. How do small single-domain proteins fold?. Fold. Des. 3 (1998) R81-R91
    • (1998) Fold. Des. , vol.3
    • Jackson, S.E.1
  • 24
    • 0030950608 scopus 로고    scopus 로고
    • Modular peptide recognition domains in eukaryotic signaling
    • Kuriyan J., and Cowburn D. Modular peptide recognition domains in eukaryotic signaling. Annu. Rev. Biophys. Biomol. Struct. 26 (1997) 259-288
    • (1997) Annu. Rev. Biophys. Biomol. Struct. , vol.26 , pp. 259-288
    • Kuriyan, J.1    Cowburn, D.2
  • 25
    • 0028895654 scopus 로고
    • Modular binding domains in signal transduction proteins
    • Cohen G.B., Ren R., and Baltimore D. Modular binding domains in signal transduction proteins. Cell 80 (1995) 237-248
    • (1995) Cell , vol.80 , pp. 237-248
    • Cohen, G.B.1    Ren, R.2    Baltimore, D.3
  • 26
    • 0035030510 scopus 로고    scopus 로고
    • SH3 domains: complexity in moderation
    • Mayer B.J. SH3 domains: complexity in moderation. J. Cell. Sci. 114 (2001) 1253-1263
    • (2001) J. Cell. Sci. , vol.114 , pp. 1253-1263
    • Mayer, B.J.1
  • 27
    • 0036420970 scopus 로고    scopus 로고
    • How SH3 domains recognize proline
    • Musacchio A. How SH3 domains recognize proline. Adv. Protein Chem. 61 (2002) 211-268
    • (2002) Adv. Protein Chem. , vol.61 , pp. 211-268
    • Musacchio, A.1
  • 28
    • 0025765803 scopus 로고
    • SH2 and SH3 domains: elements that control interactions of cytoplasmic signaling proteins
    • Koch C.A., Anderson D., Moran M.F., Ellis C., and Pawson T. SH2 and SH3 domains: elements that control interactions of cytoplasmic signaling proteins. Science 252 (1991) 668-674
    • (1991) Science , vol.252 , pp. 668-674
    • Koch, C.A.1    Anderson, D.2    Moran, M.F.3    Ellis, C.4    Pawson, T.5
  • 29
    • 0036172116 scopus 로고    scopus 로고
    • Hydrophobic core packing in the SH3 domain folding transition state
    • Northey J.G., Di Nardo A.A., and Davidson A.R. Hydrophobic core packing in the SH3 domain folding transition state. Nat. Struct. Biol. 9 (2002) 126-130
    • (2002) Nat. Struct. Biol. , vol.9 , pp. 126-130
    • Northey, J.G.1    Di Nardo, A.A.2    Davidson, A.R.3
  • 30
    • 0029760326 scopus 로고    scopus 로고
    • Different folding transition states may result in the same native structure
    • Viguera A.R., Serrano L., and Wilmanns M. Different folding transition states may result in the same native structure. Nat. Struct. Biol. 3 (1996) 874-880
    • (1996) Nat. Struct. Biol. , vol.3 , pp. 874-880
    • Viguera, A.R.1    Serrano, L.2    Wilmanns, M.3
  • 31
    • 2342451295 scopus 로고    scopus 로고
    • Transition states for protein folding have native topologies despite high structural variability
    • Lindorff-Larsen K., Vendruscolo M., Paci E., and Dobson C.M. Transition states for protein folding have native topologies despite high structural variability. Nat. Struct. Mol. Biol. 11 (2004) 443-449
    • (2004) Nat. Struct. Mol. Biol. , vol.11 , pp. 443-449
    • Lindorff-Larsen, K.1    Vendruscolo, M.2    Paci, E.3    Dobson, C.M.4
  • 32
    • 13844299144 scopus 로고    scopus 로고
    • The family feud: do proteins with similar structures fold via the same pathway?
    • Zarrine-Afsar A., Larson S.M., and Davidson A.R. The family feud: do proteins with similar structures fold via the same pathway?. Curr. Opin. Struct. Biol. 15 (2005) 42-49
    • (2005) Curr. Opin. Struct. Biol. , vol.15 , pp. 42-49
    • Zarrine-Afsar, A.1    Larson, S.M.2    Davidson, A.R.3
  • 33
    • 33748675500 scopus 로고    scopus 로고
    • Abp1p and Fyn SH3 domains fold through similar low-populated intermediate states
    • Korzhnev D.M., Neudecker P., Zarrine-Afsar A., Davidson A.R., and Kay L.E. Abp1p and Fyn SH3 domains fold through similar low-populated intermediate states. Biochemistry 45 (2006) 10175-10183
    • (2006) Biochemistry , vol.45 , pp. 10175-10183
    • Korzhnev, D.M.1    Neudecker, P.2    Zarrine-Afsar, A.3    Davidson, A.R.4    Kay, L.E.5
  • 35
    • 0037154268 scopus 로고    scopus 로고
    • Protein folding mediated by solvation: water expulsion and formation of the hydrophobic core occur after the structural collapse
    • Cheung M.S., Garcia A.E., and Onuchic J.N. Protein folding mediated by solvation: water expulsion and formation of the hydrophobic core occur after the structural collapse. Proc. Natl Acad. Sci. USA 99 (2002) 685-690
    • (2002) Proc. Natl Acad. Sci. USA , vol.99 , pp. 685-690
    • Cheung, M.S.1    Garcia, A.E.2    Onuchic, J.N.3
  • 36
    • 0037058992 scopus 로고    scopus 로고
    • Probing the folding free energy landscape of the Src-SH3 protein domain
    • Shea J.E., Onuchic J.N., and Brooks III C.L. Probing the folding free energy landscape of the Src-SH3 protein domain. Proc. Natl Acad. Sci. USA 99 (2002) 16064-16068
    • (2002) Proc. Natl Acad. Sci. USA , vol.99 , pp. 16064-16068
    • Shea, J.E.1    Onuchic, J.N.2    Brooks III, C.L.3
  • 37
    • 33645834303 scopus 로고    scopus 로고
    • New tools provide new insights in NMR studies of protein dynamics
    • Mittermaier A., and Kay L.E. New tools provide new insights in NMR studies of protein dynamics. Science 312 (2006) 224-228
    • (2006) Science , vol.312 , pp. 224-228
    • Mittermaier, A.1    Kay, L.E.2
  • 38
    • 33645073892 scopus 로고    scopus 로고
    • Partial unfolding of diverse SH3 domains on a wide timescale
    • Wales T.E., and Engen J.R. Partial unfolding of diverse SH3 domains on a wide timescale. J. Mol. Biol. 357 (2006) 1592-1604
    • (2006) J. Mol. Biol. , vol.357 , pp. 1592-1604
    • Wales, T.E.1    Engen, J.R.2
  • 39
    • 0027191192 scopus 로고
    • Solution structure and ligand-binding site of the SH3 domain of the p85 alpha subunit of phosphatidylinositol 3-kinase
    • Booker G.W., Gout I., Downing A.K., Driscoll P.C., Boyd J., Waterfield M.D., and Campbell I.D. Solution structure and ligand-binding site of the SH3 domain of the p85 alpha subunit of phosphatidylinositol 3-kinase. Cell 73 (1993) 813-822
    • (1993) Cell , vol.73 , pp. 813-822
    • Booker, G.W.1    Gout, I.2    Downing, A.K.3    Driscoll, P.C.4    Boyd, J.5    Waterfield, M.D.6    Campbell, I.D.7
  • 40
    • 0032570543 scopus 로고    scopus 로고
    • Folding kinetics of the SH3 domain of PI3 kinase by real-time NMR combined with optical spectroscopy
    • Guijarro J.I., Morton C.J., Plaxco K.W., Campbell I.D., and Dobson C.M. Folding kinetics of the SH3 domain of PI3 kinase by real-time NMR combined with optical spectroscopy. J. Mol. Biol. 276 (1998) 657-667
    • (1998) J. Mol. Biol. , vol.276 , pp. 657-667
    • Guijarro, J.I.1    Morton, C.J.2    Plaxco, K.W.3    Campbell, I.D.4    Dobson, C.M.5
  • 41
    • 0036307492 scopus 로고    scopus 로고
    • Burst-phase expansion of native protein prior to global unfolding in SDS
    • Otzen D.E., and Oliveberg M. Burst-phase expansion of native protein prior to global unfolding in SDS. J. Mol. Biol. 315 (2002) 1231-1240
    • (2002) J. Mol. Biol. , vol.315 , pp. 1231-1240
    • Otzen, D.E.1    Oliveberg, M.2
  • 42
    • 34247859221 scopus 로고    scopus 로고
    • Equilibrium and kinetics of the folding and unfolding of canine milk lysozyme
    • Nakatani H., Maki K., Saeki K., Aizawa T., Demura M., Kawano K., et al. Equilibrium and kinetics of the folding and unfolding of canine milk lysozyme. Biochemistry 46 (2007) 5238-5251
    • (2007) Biochemistry , vol.46 , pp. 5238-5251
    • Nakatani, H.1    Maki, K.2    Saeki, K.3    Aizawa, T.4    Demura, M.5    Kawano, K.6
  • 43
    • 0036298969 scopus 로고    scopus 로고
    • Folding of the yeast prion protein Ure2: kinetic evidence for folding and unfolding intermediates
    • Galani D., Fersht A.K., and Perrett S. Folding of the yeast prion protein Ure2: kinetic evidence for folding and unfolding intermediates. J. Mol. Biol. 315 (2002) 213-227
    • (2002) J. Mol. Biol. , vol.315 , pp. 213-227
    • Galani, D.1    Fersht, A.K.2    Perrett, S.3
  • 44
    • 0000949875 scopus 로고    scopus 로고
    • Evidence for at Least two native forms of rabbit muscle adenylate kinase in equilibrium in aqueous solution
    • Zhang H.J., Sheng X.R., Niu W.D., Pan X.M., and Zhou J.M. Evidence for at Least two native forms of rabbit muscle adenylate kinase in equilibrium in aqueous solution. J. Biol. Chem. 237 (1998) 7448-7456
    • (1998) J. Biol. Chem. , vol.237 , pp. 7448-7456
    • Zhang, H.J.1    Sheng, X.R.2    Niu, W.D.3    Pan, X.M.4    Zhou, J.M.5
  • 45
    • 0030882667 scopus 로고    scopus 로고
    • Thermodynamics of the complex protein unfolding reaction of barstar
    • Agashe V.R., Schmid F.X., and Udgaonkar J.B. Thermodynamics of the complex protein unfolding reaction of barstar. Biochemistry 36 (1997) 12288-12295
    • (1997) Biochemistry , vol.36 , pp. 12288-12295
    • Agashe, V.R.1    Schmid, F.X.2    Udgaonkar, J.B.3
  • 46
    • 0035812628 scopus 로고    scopus 로고
    • Folding of horse cytochrome c in reduced state
    • Bhuyan A.K., and Udgaonkar J.B. Folding of horse cytochrome c in reduced state. J. Mol. Biol. 312 (2001) 1135-1160
    • (2001) J. Mol. Biol. , vol.312 , pp. 1135-1160
    • Bhuyan, A.K.1    Udgaonkar, J.B.2
  • 47
    • 33846617642 scopus 로고    scopus 로고
    • Diffusional barrier in the unfolding of a small protein
    • Pradeep L., and Udgaonkar J.B. Diffusional barrier in the unfolding of a small protein. J. Mol. Biol. 366 (2007) 1016-1028
    • (2007) J. Mol. Biol. , vol.366 , pp. 1016-1028
    • Pradeep, L.1    Udgaonkar, J.B.2
  • 48
    • 0030664958 scopus 로고    scopus 로고
    • An early intermediate in the folding reaction of the B1 domain of protein G contains a native-like core
    • Park S.H., O'Neil K.T., and Roder H. An early intermediate in the folding reaction of the B1 domain of protein G contains a native-like core. Biochemistry 36 (1997) 14277-14283
    • (1997) Biochemistry , vol.36 , pp. 14277-14283
    • Park, S.H.1    O'Neil, K.T.2    Roder, H.3
  • 49
    • 3342900252 scopus 로고    scopus 로고
    • Localized nature of the transition-state structure in goat α-lactalbumin folding
    • Saeki K., Arai M., Yoda T., Nakao M., and Kuwajima K. Localized nature of the transition-state structure in goat α-lactalbumin folding. J. Mol. Biol. 341 (2004) 589-604
    • (2004) J. Mol. Biol. , vol.341 , pp. 589-604
    • Saeki, K.1    Arai, M.2    Yoda, T.3    Nakao, M.4    Kuwajima, K.5
  • 51
    • 1842635616 scopus 로고    scopus 로고
    • Thermodynamic characterisation of two transition states along parallel protein folding pathways
    • Wright C.F., Steward A., and Clarke J. Thermodynamic characterisation of two transition states along parallel protein folding pathways. J. Mol. Biol. 338 (2004) 445-451
    • (2004) J. Mol. Biol. , vol.338 , pp. 445-451
    • Wright, C.F.1    Steward, A.2    Clarke, J.3
  • 53
    • 0037974485 scopus 로고    scopus 로고
    • Posttransition state desolvation of the hydrophobic core of the src-SH3 protein domain
    • Guo W., Lampoudi S., and Shea J.E. Posttransition state desolvation of the hydrophobic core of the src-SH3 protein domain. Biophys. J. 85 (2003) 61-69
    • (2003) Biophys. J. , vol.85 , pp. 61-69
    • Guo, W.1    Lampoudi, S.2    Shea, J.E.3
  • 54
    • 0028915773 scopus 로고
    • Perturbation of a tertiary hydrogen bond in barstar by mutagenesis of the sole His residue to Gln leads to accumulation of at least one equilibrium folding intermediate
    • Nath U., and Udgaonkar J.B. Perturbation of a tertiary hydrogen bond in barstar by mutagenesis of the sole His residue to Gln leads to accumulation of at least one equilibrium folding intermediate. Biochemistry 34 (1995) 1702-1713
    • (1995) Biochemistry , vol.34 , pp. 1702-1713
    • Nath, U.1    Udgaonkar, J.B.2
  • 55
    • 0017282561 scopus 로고
    • A quantitative treatment of the kinetics of the folding transition of ribonuclease A
    • Hagerman P.L., and Baldwin R.L. A quantitative treatment of the kinetics of the folding transition of ribonuclease A. Biochemistry 15 (1976) 1462-1473
    • (1976) Biochemistry , vol.15 , pp. 1462-1473
    • Hagerman, P.L.1    Baldwin, R.L.2


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