An expanding arsenal of experimental methods yields an explosion of insights into protein folding mechanisms

Nature Structural and Molecular Biology

Volumn 16, Issue 6, 2009, Pages 582-588

  Bartlett, Alice I ^a   Radford, Sheena E ^a  

^a UNIVERSITY OF LEEDS   (United Kingdom)

Author keywords

[No Author keywords available]

Indexed keywords

8 ANILINO 1 NAPHTHALENESULFONIC ACID; CHAPERONE; POLYPEPTIDE; PROTEIN S6; RETINOIC ACID BINDING PROTEIN;

ANALYTIC METHOD; ANISOTROPY; CIRCULAR DICHROISM; ELECTROSPRAY MASS SPECTROMETRY; ENTROPY; ESCHERICHIA COLI; EXPERIMENTAL STUDY; FLUORESCENCE RESONANCE ENERGY TRANSFER; INFRARED SPECTROSCOPY; INTRINSIC TRYPTOPHAN FLUORESCENCE; NONHUMAN; NUCLEAR MAGNETIC RESONANCE SPECTROSCOPY; PRIORITY JOURNAL; PROTEIN ANALYSIS; PROTEIN CONFORMATION; PROTEIN ENGINEERING; PROTEIN FOLDING; PROTEIN INTERACTION; PROTEIN STRUCTURE; RAMAN SPECTROMETRY; REVIEW; SYNCHROTRON; X RAY CRYSTALLOGRAPHY; XENOPUS LAEVIS;

CIRCULAR DICHROISM; ENTROPY; FLUORESCENCE RESONANCE ENERGY TRANSFER; MAGNETIC RESONANCE SPECTROSCOPY; MODELS, CHEMICAL; MODELS, MOLECULAR; PROTEIN CONFORMATION; PROTEIN FOLDING; PROTEIN STRUCTURE, SECONDARY; PROTEINS;

EID: 66849106554     PISSN: 15459993     EISSN: 15459985     Source Type: Journal    
DOI: 10.1038/nsmb.1592     Document Type: Review

References (107)

1. Fersht, A.R. From the first protein structures to our current knowledge of protein folding: delights and scepticisms. Nat. Rev. Mol. Cell Biol. 9, 650-654 (2008).
2. Kubelka, J., Hofrichter, J. & Eaton, W.A. The protein folding 'speed limit'. Curr. Opin. Struct. Biol. 14, 76-88 (2004).
3. Karplus, M. The Levinthal paradox: yesterday and today. Fold. Des. 2, S69-S75 (1997).
4. Brockwell, D.J. & Radford, S.E. Intermediates: ubiquitous species on folding energy landscapes? Curr. Opin. Struct. Biol. 17, 30-37 (2007).
5. Bryngelson, J.D., Onuchic, J.N., Socci, N.D. & Wolynes, P.G. Funnels, pathways, and the energy landscape of protein-folding - a synthesis. Proteins 21, 167-195 (1995).
6. Onuchic, J.N. & Wolynes, P.G. Theory of protein folding. Curr. Opin. Struct. Biol. 14, 70-75 (2004).
7. Ferreiro, D.U., Hegler, J.A., Komives, E.A. & Wolynes, P.G. Localizing frustration in native proteins and protein assemblies. Proc. Natl. Acad. Sci. USA 104, 19819-19824 (2007).
8. Hagen, S.J. Probe-dependent and nonexponential relaxation kinetics: unreliable signatures of downhill protein folding. Proteins 68, 205-217 (2007).
9. Gruebele, M. Comment on probe-dependent and nonexponential relaxation kinetics: unreliable signatures of 'downhill' protein folding. Proteins 70, 1099-1102 (2008).
10. Knott, M. & Chan, H.S. Criteria for downhill protein folding: calorimetry, chevron plot, kinetic relaxation, and single-molecule radius of gyration in chain models with subdued degrees of cooperativity. Proteins 65, 373-391 (2006).
11. Ferguson, N., Sharpe, T.D., Johnson, C.M., Schartau, P.J. & Fersht, A.R. Structural biology - analysis of 'downhill' protein folding. Nature 445, E14-E15 (2007).
12. Zhou, Z. & Bai, Y.W. Structural biology - analysis of protein-folding cooperativity. Nature 445, E16-E17 (2007).
13. Ma, H. & Gruebele, M. Kinetics are probe-dependent during downhill folding of an engineered lambda(6-85) protein. Proc. Natl. Acad. Sci. USA 102, 2283-2287 (2005).
14. Sadqi, M., Fushman, D. & Munoz, V. Atom-by-atom analysis of global downhill protein folding. Nature 442, 317-321 (2006).
15. Fung, A., Li, P., Godoy-Ruiz, R., Sanchez-Ruiz, J.M. & Munoz, V. Expanding the realm of ultrafast protein folding: gpW, a midsize natural single-domain with α+β topology that folds downhill. J. Am. Chem. Soc. 130, 7489-7495 (2008).
16. Huang, F., Sato, S., Sharpe, T.D., Ying, L.M. & Fersht, A.R. Distinguishing between cooperative and unimodal downhill protein folding. Proc. Natl. Acad. Sci. USA 104, 123-127 (2007).
17. Schuler, B. & Eaton, W.A. Protein folding studied by single-molecule FRET. Curr. Opin. Struct. Biol. 18, 16-26 (2008).
18. Dyer, R.B. Ultrafast and downhill protein folding. Curr. Opin. Struct. Biol. 17, 38-47 (2007).
19. Religa, T.L., Markson, J.S., Mayor, U., Freund, S.M.V. & Fersht, A.R. Solution structure of a protein denatured state and folding intermediate. Nature 437, 1053-1056 (2005).
20. Gsponer, J. et al. Determination of an ensemble of structures representing the intermediate state of the bacterial immunity protein Im7. Proc. Natl. Acad. Sci. USA 103, 99-104 (2006).
21. Friel, C.T., Smith, D.A., Vendruscolo, M., Gsponer, J. & Radford, S.E. The mechanism of formation of a folding intermediate reveals the competition between functional and kinetic evolutionary constraints. Nat. Struct. Mol. Biol. 16, 318-324 (2009).
22. Salvatella, X., Dobson, C.M., Fersht, A.R. & Vendruscolo, M. Determination of the folding transition states of barnase by using phi(I)-value-restrained simulations validated by double mutant phi(IJ)-values. Proc. Natl. Acad. Sci. USA 102, 12389-12394 (2005).
23. Calosci, N. et al. Comparison of successive transition states for folding reveals alternative early folding pathways of two homologous proteins. Proc. Natl. Acad. Sci. USA 105, 19241-19246 (2008).
24. Korzhnev, D.M. et al. Low-populated folding intermediates of Fyn SH3 characterized by relaxation dispersion NMR. Nature 430, 586-590 (2004).
25. Neudecker, P., Zarrine-Afsar, A., Davidson, A.R. & Kay, L.E. Phi-value analysis of a three-state protein folding pathway by NMR relaxation dispersion spectroscopy. Proc. Natl. Acad. Sci. USA 104, 15717-15722 (2007).
26. Roder, H., Maki, K. & Cheng, H. Early events in protein folding explored by rapid mixing methods. Chem. Rev. 106, 1836-1861 (2006).
27. Dill, K.A., Ozkan, S.B., Shell, M.S. & Weikl, T.R. The protein folding problem. Annu. Rev. Biophys. 37, 289-316 (2008).
28. Korzhnev, D.M. & Kay, L.E. Probing invisible, low-populated states of protein molecules by relaxation dispersion NMR spectroscopy: an application to protein folding. Acc. Chem. Res. 41, 442-451 (2008).
29. Nettels, D., Hoffmann, A. & Schuler, B. Unfolded protein and peptide dynamics investigated with single-molecule FRET and correlation spectroscopy from picoseconds to seconds. J. Phys. Chem. B 112, 6137-6146 (2008).
30. Hoffmann, A. et al. Mapping protein collapse with single-molecule fluorescence and kinetic synchrotron radiation circular dichroism spectroscopy. Proc. Natl. Acad. Sci. USA 104, 105-110 (2007).
31. Várnai, P., Dobson, C.M. & Vendruscolo, M. Determination of the transition state ensemble for the folding of ubiquitin from a combination of Phi and Psi analyses. J. Mol. Biol. 377, 575-588 (2008).
32. Allen, L.R. & Paci, E. Transition states for protein folding using molecular dynamics and experimental restraints. J. Phys. Condens. Matter 19, 285211 (2007).
33. van Gunsteren, W.F., Dolenc, J. & Mark, A.E. Molecular simulation as an aid to experimentalists. Curr. Opin. Struct. Biol. 18, 149-153 (2008).
34. Oroguchi, T. et al. Atomically detailed description of the unfolding of α-lactalbumin by the combined use of experiments and simulations. J. Mol. Biol. 354, 164-172 (2005).
35. Marsh, J.A. et al. Improved structural characterizations of the drkN SH3 domain unfolded state suggest a compact ensemble with native-like and non-native structure. J. Mol. Biol. 367, 1494-1510 (2007).
36. Chugha, P. & Oas, T.G. Backbone dynamics of the monomeric l repressor denatured state ensemble under nondenaturing conditions. Biochemistry 46, 1141-1151 (2007).
37. Le Duff, C.S., Whittaker, S.B.M., Radford, S.E. & Moore, G.R. Characterisation of the conformational properties of urea-unfolded Im7: implications for the early stages of protein folding. J. Mol. Biol. 364, 824-835 (2006).
38. Kristjansdottir, S. et al. Formation of native and non-native interactions in ensembles of denatured ACBP molecules from paramagnetic relaxation enhancement studies. J. Mol. Biol. 347, 1053-1062 (2005).
39. Kohn, J.E. et al. Random-coil behavior and the dimensions of chemically unfolded proteins. Proc. Natl. Acad. Sci. USA 101, 12491-12496 (2004).
40. Fierz, B. et al. Loop formation in unfolded polypeptide chains on the picoseconds to microseconds time scale. Proc. Natl. Acad. Sci. USA 104, 2163-2168 (2007).
41. Fersht, A.R., Matouschek, A. & Serrano, L. The folding of an enzyme: I. Theory of protein engineering analysis of stability and pathway of protein folding. J. Mol. Biol. 224, 771-782 (1992).
42. Zarrine-Afsar, A. & Davidson, A.R. The analysis of protein folding kinetic data produced in protein engineering experiments. Methods 34, 41-50 (2004).
43. Sánchez, I.E. & Kiefhaber, T. Origin of unusual φ-values in protein folding: evidence against specific nucleation sites. J. Mol. Biol. 334, 1077-1085 (2003).
44. Fersht, A.R. & Sato, S. F-value analysis and the nature of protein-folding transition states. Proc. Natl. Acad. Sci. USA 101, 7976-7981 (2004).
45. Cho, J.-H. & Raleigh, D.P. Denatured state effects and the origin of nonclassical values in protein folding. J. Am. Chem. Soc. 128, 16492-16493 (2006).
46. Dobson, C.M. Protein folding and misfolding. Nature 426, 884-890 (2003).
47. Zhou, Z. & Bai, Y. Detection of a hidden folding intermediate in the focal adhesion target domain: implications for its function and folding. Proteins 65, 259-265 (2006).
48. Rhoades, E., Cohen, M., Schuler, B. & Haran, G. Two-state folding observed in individual protein molecules. J. Am. Chem. Soc. 126, 14686-14687 (2004).
49. Kuzmenkina, E.V., Heyes, C.D. & Nienhaus, G.U. Single-molecule Förster resonance energy transfer study of protein dynamics under denaturing conditions. Proc. Natl. Acad. Sci. USA 102, 15471-15476 (2005).
50. Cecconi, C., Shank, E.A., Bustamante, C. & Marqusee, S. Direct observation of the three-state folding of a single protein molecule. Science 309, 2057-2060 (2005).
51. Mickler, M. et al. Revealing the bifurcation in the unfolding pathways of GFP by using single-molecule experiments and simulations. Proc. Natl. Acad. Sci. USA 104, 20268-20273 (2007).
52. Zarrine-Afsar, A., Larson, S.M. & Davidson, A.R. The family feud: do proteins with similar structures fold via the same pathway? Curr. Opin. Struct. Biol. 15, 42-49 (2005).
53. Spudich, G.M., Miller, E.J. & Marqusee, S. Destabilization of the Escherichia coli RNase H kinetic intermediate: switching between a two-state and three-state folding mechanism. J. Mol. Biol. 335, 609-618 (2004).
54. Plaxco, K.W., Simons, K.T. & Baker, D. Contact order, transition state placement and the refolding rates of single domain proteins. J. Mol. Biol. 277, 985-994 (1998).
55. Jackson, S.E. & Fersht, A.R. Folding of chymotrypsin inhibitor 2. 1. Evidence for a two-state transition. Biochemistry 30, 10428-10435 (1991).
56. Radford, S.E., Dobson, C.M. & Evans, P.A. The folding of hen lysozyme involves partially structured intermediates and multiple pathways. Nature 358, 302-307 (1992).
57. Wright, C.F., Lindorff-Larsen, K., Randles, L.G. & Clarke, J. Parallel protein-unfolding pathways revealed and mapped. Nat. Struct. Mol. Biol. 10, 658-662 (2003).
58. Eckert, B., Martin, A., Balbach, J. & Schmid, F.X. Prolyl isomerization as a molecular timer in phage infection. Nat. Struct. Mol. Biol. 12, 619-623 (2005).
59. Crespo, M.D., Simpson, E.R. & Searle, M.S. Population of on-pathway intermediates in the folding of ubiquitin. J. Mol. Biol. 360, 1053-1066 (2006).
60. Weissman, J.S. & Kim, P.S. A kinetic explanation for the rearrangement pathway of BPTI folding. Nat. Struct. Biol. 2, 1123-1130 (1995).
61. Lindberg, M.O. & Oliveberg, M. Malleability of protein folding pathways: a simple reason for complex behaviour. Curr. Opin. Struct. Biol. 17, 21-29 (2007).
62. Lindberg, M.O., Haglund, E., Hubner, I.A., Shakhnovich, E.I. & Oliveberg, M. Identification of the minimal protein-folding nucleus through loop-entropy perturbations. Proc. Natl. Acad. Sci. USA 103, 4083-4088 (2006).
63. Haglund, E., Lindberg, M.O. & Oliveberg, M. Changes of protein folding pathways by circular permutation - overlapping nuclei promote global cooperativity. J. Biol. Chem. 283, 27904-27915 (2008).
64. Ferreiro, D.U., Walczak, A.M., Komives, E.A. & Wolynes, P.G. The energy landscapes of repeat-containing proteins: topology, cooperativity, and the folding funnels of one-dimensional architectures. PLOS Comput. Biol. 4, e1000070 (2008).
65. Lowe, A.R. & Itzhaki, L.S. Rational redesign of the folding pathway of a modular protein. Proc. Natl. Acad. Sci. USA 104, 2679-2684 (2007).
66. Tripp, K.W. & Barrick, D. Rerouting the folding pathway of the notch ankyrin domain by reshaping the energy landscape. J. Am. Chem. Soc. 130, 5681-5688 (2008).
67. Watters, A.L. et al. The highly cooperative folding of small naturally occurring proteins is likely the result of natural selection. Cell 128, 613-624 (2007).
68. Tartaglia, G.G., Pechmann, S., Dobson, C.M. & Vendruscolo, M. Life on the edge: a link between gene expression levels and aggregation rates of human proteins. Trends Biochem. Sci. 32, 204-206 (2007).
69. Jäger, M. et al. Structure-function-folding relationship in a WW domain. Proc. Natl. Acad. Sci. USA 103, 10648-10653 (2006).
70. Gosavi, S., Whitford, P.C., Jennings, P.A. & Onuchic, J.N. Extracting function from a b-trefoil folding motif. Proc. Natl. Acad. Sci. USA 105, 10384-10389 (2008).
71. Capraro, D.T., Roy, M., Onuchic, J.N. & Jennings, P.A. Backtracking on the folding landscape of the b-trefoil protein interleukin-1β? Proc. Natl. Acad. Sci. USA 105, 14844-14848 (2008).
72. Balch, W.E., Morimoto, R.I., Dillin, A. & Kelly, J.W. Adapting proteostasis for disease intervention. Science 319, 916-919 (2008).
73. Ellis, R.J. Macromolecular crowding: obvious but underappreciated. Trends Biochem. Sci. 26, 597-604 (2001).
74. Saibil, H.R. Chaperone machines in action. Curr. Opin. Struct. Biol. 18, 35-42 (2008).
75. Charlton, L.M. et al. Residue-level interrogation of macromolecular crowding effects on protein stability. J. Am. Chem. Soc. 130, 6826-6830 (2008).
76. Engel, R. et al. Macromolecular crowding compacts unfolded apoflavodoxin and causes severe aggregation of the off-pathway intermediate during apoflavodoxin folding. J. Biol. Chem. 283, 27383-27394 (2008).
77. Zhou, H.-X., Rivas, G. & Minton, A.P. Macromolecular crowding and confinement: biochemical, biophysical, and potential physiological consequences. Annu. Rev. Biophys. 37, 375-397 (2008).
78. Mittal, J. & Best, R.B. Thermodynamics and kinetics of protein folding under confinement. Proc. Natl. Acad. Sci. USA 105, 20233-20238 (2008).
79. Cheung, M.S. & Thirumalai, D. Effects of crowding and confinement on the structures of the transition state ensemble in proteins. J. Phys. Chem. B 111, 8250-8257 (2007).
80. Homouz, D., Perham, M., Samiotakis, A., Cheung, M.S. & Wittung-Stafshede, P. Crowded, cell-like environment induces shape changes in aspherical protein. Proc. Natl. Acad. Sci. USA 105, 11754-11759 (2008).
81. Hartl, F.U. & Hayer-Hartl, M. Converging concepts of protein folding in vitro and in vivo. Nat. Struct. Mol. Biol. 16, 574-581 (2009).
82. Kramer, G., Boehringer, D., Ban, N. & Bukau, B. The ribosome as a platform for cotranslational processing, folding and targeting of newly synthesized proteins. Nat. Struct. Mol. Biol. 16, 589-597 (2009).
83. Hsu, S.-T.D. et al. Structure and dynamics of a ribosome-bound nascent chain by NMR spectroscopy. Proc. Natl. Acad. Sci. USA 104, 16516-16521 (2007).
84. James, J.R. et al. Single-molecule level analysis of the subunit composition of the T cell receptor on live T cells. Proc. Natl. Acad. Sci. USA 104, 17662-17667 (2007).
85. Elf, J., Li, G.-W. & Xie, X.S. Probing transcription factor dynamics at the single-molecule level in a living cell. Science 316, 1191-1194 (2007).
86. Woolhead, C.A., McCormick, P.J. & Johnson, A.E. Nascent membrane and secretory proteins differ in FRET-detected folding far inside the ribosome and in their exposure to ribosomal proteins. Cell 116, 725-736 (2004).
87. Hillger, F. et al. Probing protein-chaperone interactions with single-molecule fluorescence spectroscopy. Angew. Chem. Int. Ed. Engl. 47, 6184-6188 (2008).
88. Sharma, S. et al. Monitoring protein conformation along the pathway of chaperonin-assisted folding. Cell 133, 142-153 (2008).
89. McNulty, B.C., Young, G.B. & Pielak, G.J. Macromolecular crowding in the Escherichia coli periplasm maintains alpha;-synuclein disorder. J. Mol. Biol. 355, 893-897 (2006).
90. Selenko, P., Serber, Z., Gadea, B., Ruderman, J. & Wagner, G. Quantitative NMR analysis of the protein G B1 domain in Xenopus laevis egg extracts and intact oocytes. Proc. Natl. Acad. Sci. USA 103, 11904-11909 (2006).
91. Ignatova, Z. & Gierasch, L.M. Monitoring protein stability and aggregation in vivo by real-time fluorescent labeling. Proc. Natl. Acad. Sci. USA 101, 523-528 (2004).
92. Ignatova, Z. & Gierasch, L.M. Inhibition of protein aggregation in vitro and in vivo by a natural osmoprotectant. Proc. Natl. Acad. Sci. USA 103, 13357-13361 (2006).
93. Horst, R., Fenton, W.A., Englander, S.W., Wüthrich, K. & Horwich, A.L. Folding trajectories of human dihydrofolate reductase inside the GroEL-GroES chaperonin cavity and free in solution. Proc. Natl. Acad. Sci. USA 104, 20788-20792 (2007).
94. Dennis, C.A. et al. A structural comparison of the colicin immunity proteins Im7 and Im9 gives new insights into the molecular determinants of immunity-protein specificity. Biochem. J. 333, 183-191 (1998).
95. Noble, M.E.M., Musacchio, A., Saraste, M., Courtneidge, S.A. & Wierenga, R.K. Crystal structure of the SH3 domain in human Fyn - comparison of the three-dimensional structures of SH3 domains in tyrosine kinases and spectrin. EMBO J. 12, 2617-2624 (1993).
96. Lindahl, M. et al. Crystal structure of the ribosomal protein S6 from Thermus thermophilus. EMBO J. 13, 1249-1254 (1994).
97. Royer, C.A. Probing protein folding and conformational transitions with fluorescence. Chem. Rev. 106, 1769-1784 (2006).
98. Kelly, S.M., Jess, T.J. & Price, N.C. How to study proteins by circular dichroism. Biochim. Biophys. Acta 1751, 119-139 (2005).
99. Balakrishnan, G., Weeks, C.L., Ibrahim, M., Soldatova, A.V. & Spiro, T.G. Protein dynamics from time resolved UV Raman spectroscopy. Curr. Opin. Struct. Biol. 18, 623-629 (2008).
100. Fabian, H. & Naumann, D. Methods to study protein folding by stopped-flow FT-IR. Methods 34, 28-40 (2004).
101. Haustein, E. & Schwille, P. Fluorescence correlation spectroscopy: novel variations of an established technique. Annu. Rev. Biophys. Biomol. Struct. 36, 151-169 (2007).
102. Lipfert, J. & Doniach, S. Small-angle X-ray scattering from RNA, proteins, and protein complexes. Annu. Rev. Biophys. Biomol. Struct. 36, 307-327 (2007).
103. Dyson, H.J. & Wright, P.E. Elucidation of the protein folding landscape by NMR. Methods Enzymol. 394, 299-321 (2005).
104. Krishna, M.M.G., Hoang, L., Lin, Y. & Englander, S.W. Hydrogen exchange methods to study protein folding. Methods 34, 51-64 (2004).
105. Maier, C.S. & Deinzer, M.L. Protein conformations, interactions, and H/D exchange. Methods Enzymol. 402, 312-360 (2005).
106. Sakakibara, D. et al. Protein structure determination in living cells by in-cell NMR spectroscopy. Nature 458, 102-105 (2009).
107. Inomata, K. et al. High-resolution multi-dimensional NMR spectroscopy of proteins in human cells. Nature 458, 106-109 (2009).