Protein folding mechanisms: New methods and emerging ideas

Current Opinion in Structural Biology

Volumn 10, Issue 1, 2000, Pages 16-25

  Brockwell, David J ^a   Smith, D Alastair ^a   Radford, Sheena E ^a  

^a UNIVERSITY OF LEEDS   (United Kingdom)

Author keywords

[No Author keywords available]

Indexed keywords

PROTEIN;

MOLECULAR DYNAMICS; NUCLEAR MAGNETIC RESONANCE SPECTROSCOPY; PRIORITY JOURNAL; PROTEIN ANALYSIS; PROTEIN DENATURATION; PROTEIN FOLDING; REVIEW;

EID: 0033951366     PISSN: 0959440X     EISSN: None     Source Type: Journal    
DOI: 10.1016/S0959-440X(99)00043-3     Document Type: Review

References (82)

1. Dobson C.M., Karplus M. The fundamentals of protein folding: bringing together theory and experiment. Curr Opin Struct Biol. 9:1999;92-101.
2. Alm E., Baker D. Matching theory and experiment in protein folding. Curr Opin Struct Biol. 9:1999;189-196.
3. Shortle D. The denatured state (the other half of the folding equation) and its role in protein stability. FASEB J. 10:1996;27-34.
4. Dyson H.J., Wright P.E. Equilibrium NMR studies of unfolded and partially folded proteins. Nat Struct Biol. 5:1998;499-503.
5. 15N NMR spectroscopy. J Mol Biol. 288:1999;705-723.
6. Schwalbe H., Fiebig K.M., Buck M., Jones J.A., Grimshaw S.B., Spencer A., Glaser S.J., Smith L.J., Dobson C.M. Structural and dynamical properties of a denatured protein. Heteronuclear 3D NMR experiments and theoretical simulations of lysozyme in 8 M urea. Biochemistry. 36:1997;8977-8991.
7. Denisov V.P., Jonsson B.H., Halle B. Hydration of denatured and molten globule proteins. Nat Struct Biol. 6:1999;253-260. The established technique of magnetic relaxation dispersion was applied to denatured and molten globule proteins as an indirect probe of protein hydration. The authors show that the hydration of molten globule states shows no significant differences compared with that of the native state.
8. Gillespie J.R., Shortle D. Characterization of long-range structure in the denatured state of staphylococcal nuclease. II. Distance restraints from paramagnetic relaxation and calculation of an ensemble of structures. J Mol Biol. 268:1997;170-184.
9. Wrabl J., Shortle D. A model of the changes in the denatured state structure underlying m value effects in staphylococcal nuclease. Nat Struct Biol. 6:1999;876-883.
10. Mok Y.K., Kay C.M., Kay L.E., Forman-Kay J. NOE data demonstrating a compact unfolded state for an SH3 domain under non-denaturing conditions. J Mol Biol. 289:1999;619-638. In this detailed paper, an ensemble of conformations of an SH3 domain under nondenaturing conditions is described. This species is distinct from that obtained under denaturing conditions and is compact, which may limit the conformational search to the native state.
11. Grantcharova V.P., Riddle D.S., Santiago J.V., Baker D. Important role of hydrogen bonds in the structurally polarized transition state for folding of the src SH3 domain. Nat Struct Biol. 5:1998;714-720.
12. Martinez J.C., Pisabarro M.T., Serrano L. Obligatory steps in protein folding and the conformational diversity of the transition state. Nat Struct Biol. 5:1998;721-729.
13. Yi Q., Bystroff C., Rajagopal P., Klevit R.E., Baker D. Prediction and structural characterization of an independently folding substructure in the src SH3 domain. J Mol Biol. 283:1998;293-300.
14. Chiti F., Taddei N., Webster P., Hamada D., Fiaschi T., Ramponi G., Dobson C.M. Acceleration of the folding of acylphosphatase by stabilization of local secondary structure. Nat Struct Biol. 6:1999;380-387. By adding differing amounts of the co-solvent TFE, the folding of acylphosphatase is accelerated or slowed depending on the amount of native-like interactions in the unfolded state, suggesting that structure in the denatured state can affect observed folding properties.
15. Villegas V., Martinez J.C., Aviles F.X., Serrano L. Structure of the transition state in the folding process of human procarboxypeptidase A2 activation domain. J Mol Biol. 283:1998;1027-1036. Protein engineering was used to map the transition state of a mixed α/β protein. The data show that helical structure in the denatured state does not take part in the folding nucleus.
16. Blanco F.J., Serrano L., Forman-Kay J.D. High populations of non-native structures in the denatured state are compatible with the formation of the native folded state. J Mol Biol. 284:1998;1153-1164.
17. Cavagnero S., Dyson H.J., Wright P.E. Effect of H helix destabilizing mutations on the kinetic and equilibrium folding of apomyoglobin. J Mol Biol. 285:1999;269-282.
18. Jackson S.E. How do small single-domain proteins fold? Fold Des. 3:1998;R81-R91. An excellent review describing the folding properties of the two-state and three-state proteins studied to date.
19. Lorch M., Mason J.M., Clarke A.R., Parker M.J. Effects of core mutations on the folding of a β-sheet protein: implications for backbone organization in the I-state. Biochemistry. 38:1999;1377-1385. Using protein engineering, the authors demonstrate that the intermediate state in CD2 folding has a native topology and that the effect of Φ mutants correlates more with β-sheet propensity than with the stability of the native state.
20. Kuwajima K., Yamaya H., Sugai S. The burst-phase intermediate in the refolding of β-lactoglobulin studied by stopped-flow circular dichroism and absorption spectroscopy. J Mol Biol. 264:1996;806-822.
21. Dinner A.R., Karplus M. The thermodynamics and kinetics of protein folding: a lattice model analysis of multiple pathways with intermediates. J Phys Chem B. 103:1999;7976-7994.
22. Wagner C., Kiefhaber T. Intermediates can accelerate protein folding. Proc Natl Acad Sci USA. 96:1999;6716-6721.
23. Parker M.J., Lorch M., Sessions R.B., Clarke A.R. Thermodynamic properties of transient intermediates and transition states in the folding of two contrasting protein structures. Biochemistry. 37:1998;2538-2545.
24. Capaldi A.P., Ferguson S.J., Radford S.E. The Greek key protein apo-pseudoazurin folds through an obligate on-pathway intermediate. J Mol Biol. 286:1999;1621-1632.
25. Tan Y.J., Oliveberg M., Fersht A.R. Titration properties and thermodynamics of the transition state for folding-comparison of 2-state and multistate folding pathways. J Mol Biol. 264:1996;377-389.
26. Coyle J.E., Texter F.L., Ashcroft A.E., Masselos D., Robinson C.V., Radford S.E. GroEL accelerates the refolding of hen lysozyme without changing its folding mechanism. Nat Struct Biol. 6:1999;683-690.
27. Shtilerman M., Lorimer G.H., Englander S.W. Chaperonin function: folding by forced unfolding. Science. 284:1999;822-825.
28. Fink A.L. Protein aggregation: folding aggregates, inclusion bodies and amyloid. Fold Des. 3:1998;R9-R23.
29. Roder H., Colón W. Kinetic role of early intermediates in protein folding. Curr Opin Struct Biol. 7:1997;15-28.
30. Sosnick T.R., Shtilerman M.D., Mayne L., Englander S.W. Ultrafast signals in protein folding and the polypeptide contracted state. Proc Natl Acad Sci USA. 94:1997;8545-8550.
31. Qi P.X., Sosnick T.R., Englander S.W. The burst phase in ribonuclease A folding and solvent dependence of the unfolded state. Nat Struct Biol. 5:1998;882-884. The relevance of burst phase species to folding is questioned in this paper. Wild-type and a folding incompetent RNase A both showed submillisecond burst phase signals, which is postulated to reflect a shift to a different conformational ensemble under different denaturant concentrations.
32. Ferguson N., Capaldi A.P., James R., Kleanthous C., Radford S.E. Rapid folding with and without populated intermediates in the homologous four-helix proteins Im7 and Im9. J Mol Biol. 286:1999;1597-1608.
33. Eaton W.A., Muñoz V., Thompson P.A., Henry E.R., Hofrichter J. Kinetics and dynamics of loops, α-helices, β-hairpins, and fast-folding proteins. Accounts Chem Res. 31:1998;745-753.
34. Bieri O., Wirz J., Hellrung B., Schutkowski M., Drewello M., Kiefhaber T. The speed limit for protein folding measured by triplet-triplet energy transfer. Proc Natl Acad Sci USA. 96:1999;9597-9601. Laser-flash photolysis, combined with triplet-triplet energy transfer, allowed measurement of contact times between donor and acceptor groups in various lengths of peptides to be measured from 20 ns to 30 μs. This allowed an upper speed limit for the formation of sidechain contacts to be directly measured.
35. Ballew R.M., Sabelko J., Gruebele M. Direct observation of fast protein folding: the initial collapse of apomyoglobin. Proc Natl Acad Sci USA. 93:1996;5759-5764.
36. Nolting B., Golbik R., Fersht A.R. Submillisecond events in protein-folding. Proc Natl Acad Sci USA. 92:1995;10668-10672.
37. 562 folding triggered by electron transfer: approaching the speed limit for formation of a four-helix-bundle protein. Proc Natl Acad Sci USA. 96:1999;6587-6590.
38. Shastry M.C.R., Roder H. Evidence for barrier-limited protein folding kinetics on the microsecond time scale. Nat Struct Biol. 5:1998;385-392.
39. Park S-H., Shastry M.C.R., Roder H. Folding dynamics of the B1 domain of protein G explored by ultrarapid mixing. Nat Struct Biol. 6:1999;943-947. A combination of stopped-flow and continuous-flow fluorescence measurements allowed the full characterisation of the folding kinetics of a small protein. The authors postulate folding via a rapidly formed on-pathway intermediate.
40. Pollack L., Tate M.W., Darnton N.C., Knight J.B., Gruner S.M., Eaton W.A., Austin R.H. Compactness of the denatured state of a fast-folding protein measured by submillisecond small-angle X-ray scattering. Proc Natl Acad Sci USA. 96:1999;10115-10117.
41. Plaxco K.W., Millett I.S., Segel D.J., Doniach S., Baker D. Chain collapse can occur concomitantly with the rate-limiting step in protein folding. Nat Struct Biol. 6:1999;554-556.
42. Muñoz V., Thompson P.A., Hofrichter J., Eaton W.A. Folding dynamics and mechanism of β-hairpin formation. Nature. 390:1997;196-199.
43. Nagi A.D., Anderson K.S., Regan L. Using loop length variants to dissect the folding pathway of a four-helix-bundle protein. J Mol Biol. 286:1999;257-265.
44. Burton R.E., Myers J.K., Oas T.G. Protein folding dynamics: quantitative comparison between theory and experiment. Biochemistry. 37:1998;5337-5343.
45. Myers J.K., Oas T.G. Reinterpretation of GCN4-p1 folding kinetics: partial helix formation precedes dimerization in coiled coil folding. J Mol Biol. 289:1999;205-209. Diffusion collision theory was applied to the previously measured folding kinetics of the GCN4-p1 peptide and used to predict the effects of glycine mutations.
46. Pappu R.V., Weaver D.L. The early folding kinetics of apomyoglobin. Protein Sci. 7:1998;480-490.
47. Kim D.E., Yi Q., Gladwin S.T., Goldberg J.M., Baker D. The single helix in protein L is largely disrupted at the rate-limiting step in folding. J Mol Biol. 284:1998;807-815.
48. Zhou Y., Karplus M. Interpreting the folding kinetics of helical proteins. Nature. 401:1999;400-403.
49. Forge V., Wijesinha R.T., Balbach J., Brew K., Robinson C.V., Redfield C., Dobson C.M. Rapid collapse and slow structural reorganisation during the refolding of bovine α-lactalbumin. J Mol Biol. 288:1999;673-688.
50. Morozova-Roche L.A., Jones J.A., Noppe W., Dobson C.M. Independent nucleation and heterogeneous assembly of structure during folding of equine lysozyme. J Mol Biol. 289:1999;1055-1073. The refolding of equine lysozyme was characterised using a battery of biophysical techniques. Residue-specific hydrogen exchange by NMR shows the rapid formation of a compact molten globule, followed by the formation of a series of intermediates from multiple nucleation sites.
51. Harrison S.C., Durbin R. Is there a single pathway for the folding of a polypeptide chain? Proc Natl Acad Sci USA. 82:1985;4028-4030.
52. Chiti F., Taddei N., van Nuland N.A.J., Magherini F., Stefani M., Ramponi G., Dobson C.M. Structural characterization of the transition state for folding of muscle acylphosphatase. J Mol Biol. 283:1998;893-903.
53. Main E.R.G., Fulton K.F., Jackson S.E. Folding pathway of FKBP12 and characterisation of the transition state. J Mol Biol. 291:1999;429-444.
54. Oliveberg M., Fersht A.R. Formation of electrostatic interactions on the protein folding pathway. Biochemistry. 35:1996;2726-2737.
55. Dalby P.A., Oliveberg M., Fersht A.R. Movement of the intermediate and rate determining transition state of barnase on the energy landscape with changing temperature. Biochemistry. 37:1998;4674-4679.
56. Main E.R.G., Jackson S.E. Does trifluoroethanol affect folding pathways and can it be used as a probe of structure in transition states? Nat Struct Biol. 6:1999;831-835. Φ-Analysis, coupled with studies of folding/unfolding kinetics in the presence and absence of TFE, indicates that studies using co-solvents should be interpreted with caution.
57. Fersht A. Structure and Mechanism in Protein Science: A Guide to Enzyme Catalysis and Protein Folding, edn 1. 1998;WH Freeman and Company, New York. This, book includes chapters on the kinetics of protein folding, folding mechanisms and energy landscapes. These, chapters cover the theory and techniques of protein folding and describe the development of folding models based on the plethora of data on CI2, barnase and barstar.
58. Daggett V., Li A.J., Fersht A.R. Combined molecular dynamics and Φ-value analysis of structure-reactivity relationships in the transition state and unfolding pathway of barnase: structural basis of Hammond and anti-Hammond effects. J Am Chem Soc. 120:1998;12740-12754.
59. Daggett V., Li A.J., Itzhaki L.S., Otzen D.E., Fersht A.R. Structure of the transition state for folding of a protein derived from experiment and simulation. J Mol Biol. 257:1996;430-440.
60. Fulton K.F., Main E.R.G., Daggett V., Jackson S.E. Mapping the interactions present in the transition state for unfolding/folding of FKBP12. J Mol Biol. 291:1999;445-461.
61. Kragelund B.B., Osmark P., Neergaard T.B., Schiodt J., Kristiansen K., Knudsen J., Poulsen F.M. The formation of a native-like structure containing eight conserved hydrophobic residues is rate limiting in two-state protein folding of ACBP. Nat Struct Biol. 6:1999;594-601.
62. Neira J.L., Itzhaki L.S., Ladurner A.G., Davis B., Gay G.D., Fersht A.R. Following co-operative formation of secondary and tertiary structure in a single protein module. J Mol Biol. 268:1997;185-197.
63. Neira J.L., Fersht A.R. Exploring the folding funnel of a polypeptide chain by biophysical studies on protein fragments. J Mol Biol. 285:1999;1309-1333.
64. Neira J.L., Fersht A.R. Acquisition of native-like interactions in C-terminal fragments of barnase. J Mol Biol. 287:1999;421-432.
65. Shakhnovich E., Abkevich V., Ptitsyn O. Conserved residues and the mechanism of protein folding. Nature. 379:1996;96-98.
66. Viguera A.R., Serrano L., Wilmanns M. Different folding transition states may result in the same native structure. Nat Struct Biol. 3:1996;874-880.
67. Otzen D.E., Kristensen O., Proctor M., Oliveberg M. Structural changes in the transition state of protein folding: alternative interpretations of curved chevron plots. Biochemistry. 38:1999;6499-6511.
68. Ladurner A.G., Itzhaki L.S., Daggett V., Fersht A.R. Synergy between simulation and experiment in describing the energy landscape of protein folding. Proc Natl Acad Sci USA. 95:1998;8473-8478.
69. Duan Y., Kollman P.A. Pathways to a protein folding intermediate observed in a 1-microsecond simulation in aqueous solution. Science. 282:1998;740-744. An impressive molecular dynamics simulation of the folding of the villin headpiece, with explicit representation of water molecules, run over two orders of magnitude longer than previously possible. The population of a native-like metastable state was observed.
70. Fisher T.E., Oberhauser A.F., Carrion-Vazquez M., Marszalek P.E., Fernandez J.M. The study of protein mechanics with the atomic force microscope. Trends Biochem Sci. 24:1999;379-384.
71. Oberhauser A.F., Marszalek P.E., Erickson H.P., Fernandez J.M. The molecular elasticity of the extracellular matrix protein tenascin. Nature. 393:1998;181-185.
72. Rief M., Gautel M., Schemmel A., Gaub H.E. The mechanical stability of immunoglobulin and fibronectin III domains in the muscle protein titin measured by atomic force microscopy. Biophys J. 75:1998;3008-3014. This paper shows the power of mechanical unfolding in probing the differential adaptation of different FnIII and immunoglobulin domains to mechanical stress.
73. Rief M., Pascual J., Saraste M., Gaub H.E. Single molecule force spectroscopy of spectrin repeats: low unfolding forces in helix bundles. J Mol Biol. 286:1999;553-561.
74. Carrion-Vazquez M., Oberhauser A.F., Fowler S.B., Marszalek P.E., Broedel S.E., Clarke J., Fernandez J.M. Mechanical and chemical unfolding of a single protein: a comparison. Proc Natl Acad Sci USA. 96:1999;3694-3699. Protein engineering was used to construct 8- and 12-repeat homopolymers of I27. By measuring chemical and mechanical unfolding rates, the authors show that these methods probe the same transition state, which has the same height and placement.
75. Lu H., Isralewitz B., Krammer A., Vogel V., Schulten K. Unfolding of titin immunoglobulin domains by steered molecular dynamics simulation. Biophys J. 75:1998;662-671.
76. Paci E., Karplus M. Forced unfolding of fibronectin type 3 modules: an analysis by biased molecular dynamics simulations. J Mol Biol. 288:1999;441-459.
77. Krammer A., Lu H., Isralewitz B., Schulten K., Vogel V. Forced unfolding of the fibronectin type III module reveals a tensile molecular recognition switch. Proc Natl Acad Sci USA. 96:1999;1351-1356. Steered molecular dynamics was used to model the mechanical unfolding of the FnIII domain. The results show the peeling away of a single strand before global unfolding. The potential role of a mechanosensitive domain in vivo is discussed.
78. Klimov D.K., Thirumalai D. Stretching single-domain proteins: phase diagram and kinetics of force-induced unfolding. Proc Natl Acad Sci USA. 96:1999;6166-6170.
79. Kneipp K., Kneipp H., Kartha V.B., Manoharan R., Deinum G., Itzkan I., Dasari R.R., Feld M.S. Detection and identification of a single DNA base molecule using surface-enhanced Raman scattering (SERS). Phys Rev E. 57:1998;R6281-R6284.
80. Riddle D.S., Grantcharova V.P., Santiago J.V., Alm E., Ruczinski I., Baker D. Experiment and theory highlight the role of native state topology in SH3 folding. Nat Struct Biol. 6:1999;1016-1024.
81. Chiti F., Taddei N., White P.M., Bucciantini M., Magherini F., Stefani M., Dobson C.M. Mutational analysis of acylphosphatase suggests the importance of topology and contact order in protein folding. Nat Struct Biol. 6:1999;1005-1009.
82. Marszalek P.E., Hui L., Li H., Carrion-Vazquez M., Oberhauser A.F., Schulten K., Fernandez J.M. Mechanical unfolding intermediates in titin molecules. Nature. 402:1999;100-103.