1932
0

Annual Review of Biophysics

Volume 54, 2025

Collapse and Protein Folding: Should We Be Surprised That Biothermodynamics Works So Well?

  • Tobin R. Sosnick1,2 and Michael C. Baxa1
  • 1Department of Biochemistry and Molecular Biology, University of Chicago, Chicago, Illinois, USA; email: [email protected], [email protected] 2Institute for Biophysical Dynamics and Pritzker School of Molecular Engineering, University of Chicago, Chicago, Illinois, USA
  • Vol. 54:17-34 (Volume publication date May 2025)
  • First published as a Review in Advance on December 17, 2024
  • Copyright © 2025 by the author(s).
    This work is licensed under a Creative Commons Attribution 4.0 International License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. See credit lines of images or other third-party material in this article for license information.

Abstract

A complete understanding of protein function and dynamics requires the characterization of the multiple thermodynamic states, including the denatured state ensemble (DSE). Whereas residual structure in the DSE (as well as in partially folded states) is pertinent in many biological contexts, here we are interested in how such structure affects protein thermodynamics. We examine issues related to chain collapse in light of new developments, focusing on potential complications arising from differences in the DSE's properties under various conditions. Despite some variability in the degree of collapse and structure in the DSE, stability measurements are remarkably consistent between two standard methods, calorimetry and chemical denaturation, as well as with hydrogen–deuterium exchange. This robustness is due in part to the DSEs obtained with different perturbations being thermodynamically equivalent and hence able to serve as a common reference state. An examination of the properties of the DSE points to it as being a highly expanded ensemble with minimal amounts of stable hydrogen bonded structure. These two features are likely to be critical in the broad and successful application of thermodynamics to protein folding. Our review concludes with a discussion of the impact of these findings on folding mechanisms and pathways.

Keyword(s): calorimetry, denaturation, Flory exponent, Gibbs–Helmholtz equation, hydrogen–deuterium exchange, small-angle scattering
Loading

Article metrics loading...

/content/journals/10.1146/annurev-biophys-080124-123012
2025-05-06
2025-06-24
Loading full text...

Full text loading...

/deliver/fulltext/biophys/54/1/annurev-biophys-080124-123012.html?itemId=/content/journals/10.1146/annurev-biophys-080124-123012&mimeType=html&fmt=ahah

Literature Cited

  1. 1.
    Abkevich VI, Gutin AM, Shakhnovich EI. 1994.. Specific nucleus as the transition state for protein folding: evidence from the lattice model. . Biochemistry 33::10026–36
     [Crossref] [Google Scholar]
  2. 2.
    Adrover M, Esposito V, Martorell G, Pastore A, Temussi PA. 2010.. Understanding cold denaturation: the case study of Yfh1. . J. Am. Chem. Soc. 132::16240–46
     [Crossref] [Google Scholar]
  3. 3.
    Alborghetti MR, Furlan AS, Silva JC, Paes Leme AF, Torriani IC, Kobarg J. 2010.. Human FEZ1 protein forms a disulfide bond mediated dimer: implications for cargo transport. . J. Proteome Res. 9::4595–603
     [Crossref] [Google Scholar]
  4. 4.
    Arai M, Kondrashkina E, Kayatekin C, Matthews CR, Iwakura M, Bilsel O. 2007.. Microsecond hydrophobic collapse in the folding of Escherichia coli dihydrofolate reductase, an α/β-type protein. . J. Mol. Biol. 368::219–29
     [Crossref] [Google Scholar]
  5. 5.
    Babu CR, Hilser VJ, Wand AJ. 2004.. Direct access to the cooperative substructure of proteins and the protein ensemble via cold denaturation. . Nat. Struct. Mol. Biol. 11::352–57
     [Crossref] [Google Scholar]
  6. 6.
    Bai Y, Englander JJ, Mayne L, Milne JS, Englander SW. 1995.. Thermodynamic parameters from hydrogen exchange measurements. . Methods Enzymol. 259::344–56
     [Crossref] [Google Scholar]
  7. 7.
    Bai Y, Sosnick TR, Mayne L, Englander SW. 1995.. Protein folding intermediates: native-state hydrogen exchange. . Science 269::192–97
     [Crossref] [Google Scholar]
  8. 8.
    Barrick D. 2018.. Biomolecular Thermodynamics: From Theory to Application. Boca Raton, FL:: CRC Press. 524 pp.
     [Google Scholar]
  9. 9.
    Basanta B, Chan KK, Barth P, King T, Hinshaw JR, et al. 2016.. Introduction of a polar core into the de novo designed protein Top7. . Protein Sci. 25:(7):1299–307
     [Crossref] [Google Scholar]
  10. 10.
    Baxa MC, Freed KF, Sosnick TR. 2009.. ψ-constrained simulations of protein folding transition states: implications for calculating ϕ. . J. Mol. Biol. 386::920–28
     [Crossref] [Google Scholar]
  11. 11.
    Baxa MC, Haddadian EJ, Jha AK, Freed KF, Sosnick TR. 2012.. Context and force field dependence of the loss of protein back-bone entropy upon folding using realistic denatured and native state ensembles. . J. Am. Chem. Soc. 134::15929–36
     [Crossref] [Google Scholar]
  12. 12.
    Baxa MC, Haddadian EJ, Jumper JM, Freed KF, Sosnick TR. 2014.. Loss of conformational entropy in protein folding calculated using realistic ensembles and its implications for NMR-based calculations. . PNAS 111::15396–401
     [Crossref] [Google Scholar]
  13. 13.
    Baxa MC, Lin X, Mukinay CD, Chakravarthy S, Sachleben JR, et al. 2024.. How hydrophobicity, side chains, and salt affect the dimensions of disordered proteins. . Protein Sci. 33::e4986 SAXS study showing that hydrophobic interactions increase with temperature but that thermally denatured states are still expanded.
     [Crossref] [Google Scholar]
  14. 14.
    Baxa MC, Sosnick TR. 2022.. Engineered metal-binding sites to probe protein folding transition states: psi analysis. . Methods Mol. Biol. 2376::31–63 Presents the derivation of ψ analysis and its protocols and applications.
     [Crossref] [Google Scholar]
  15. 15.
    Baxa MC, Yu W, Adhikari AN, Ge L, Xia Z, et al. 2015.. Even with nonnative interactions, the updated folding transition states of the homologs proteins G & L are extensive and similar. . PNAS 112::8302–7
     [Crossref] [Google Scholar]
  16. 16.
    Becktel WJ, Schellman JA. 1987.. Protein stability curves. . Biopolymers 26::1859–77
     [Crossref] [Google Scholar]
  17. 17.
    Borgia A, Zheng W, Buholzer K, Borgia MB, Schüler A, et al. 2016.. Consistent view of polypeptide chain expansion in chemical denaturants from multiple experimental methods. . J. Am. Chem. Soc. 138::11714–26
     [Crossref] [Google Scholar]
  18. 18.
    Bosco G, Baxa M, Sosnick T. 2009.. Metal binding kinetics of bi-histidine sites used in ψ-analysis: evidence for high energy protein folding intermediates. . Biochemistry 48::2950–59
     [Crossref] [Google Scholar]
  19. 19.
    Bowman MA, Riback JA, Rodriguez A, Guo H, Li J, et al. 2020.. Properties of protein unfolded states suggest broad selection for expanded conformational ensembles. . PNAS 117::23356–64
     [Crossref] [Google Scholar]
  20. 20.
    Boze H, Marlin T, Durand D, Pérez J, Vernhet A, et al. 2010.. Proline-rich salivary proteins have extended conformations. . Biophys. J. 99::656–65
     [Crossref] [Google Scholar]
  21. 21.
    Braselmann E, Chaney JL, Clark PL. 2013.. Folding the proteome. . Trends Biochem. Sci. 38::337–44
     [Crossref] [Google Scholar]
  22. 22.
    Bressan GC, Silva JC, Borges JC, Dos Passos DO, Ramos CH, et al. 2008.. Human regulatory protein Ki-1/57 has characteristics of an intrinsically unstructured protein. . J. Proteome Res. 7::4465–74
     [Crossref] [Google Scholar]
  23. 23.
    Chamberlain AK, Handel TM, Marqusee S. 1996.. Detection of rare partially folded molecules in equilibrium with the native conformation of RNaseH. . Nat. Struct. Biol. 3::782–87
     [Crossref] [Google Scholar]
  24. 24.
    Chatterjee P, Bagchi S, Sengupta N. 2014.. The non-uniform early structural response of globular proteins to cold denaturing conditions: a case study with Yfh1. . J. Chem. Phys. 141::205103
     [Crossref] [Google Scholar]
  25. 25.
    Clark PL, Plaxco KW, Sosnick TR. 2020.. Water as a good solvent for unfolded proteins: Folding and collapse are fundamentally different. . J. Mol. Biol. 432::2882–89
     [Crossref] [Google Scholar]
  26. 26.
    Contreras-Martos S, Piai A, Kosol S, Varadi M, Bekesi A, et al. 2017.. Linking functions: an additional role for an intrinsically disordered linker domain in the transcriptional coactivator CBP. . Sci. Rep. 7::4676
     [Crossref] [Google Scholar]
  27. 27.
    D'Aquino JA, Gómez J, Hilser VJ, Lee KH, Amzel LM, Freire E. 1996.. The magnitude of the backbone conformational entropy change in protein folding. . Proteins 25::143–56
     [Crossref] [Google Scholar]
  28. 28.
    Dill KA. 1985.. Theory for the folding and stability of globular proteins. . Biochemistry 24::1501–9
     [Crossref] [Google Scholar]
  29. 29.
    Dill KA. 1990.. Dominant forces in protein folding. . Biochemistry 29::7133–55
     [Crossref] [Google Scholar]
  30. 30.
    Englander SW, Mayne L, Kan ZY, Hu W. 2016.. Protein folding—how and why: by hydrogen exchange, fragment separation, and mass spectrometry. . Annu. Rev. Biophys. 45::135–52
     [Crossref] [Google Scholar]
  31. 31.
    English LR, Tischer A, Demeler AK, Demeler B, Whitten ST. 2018.. Sequence reversal prevents chain collapse and yields heat-sensitive intrinsic disorder. . Biophys. J. 115::328–40
     [Crossref] [Google Scholar]
  32. 32.
    English LR, Voss SM, Tilton EC, Paiz EA, So S, et al. 2019.. Impact of heat on coil hydrodynamic size yields the energetics of denatured state conformational bias. . J. Phys. Chem. B 123::10014–24
     [Crossref] [Google Scholar]
  33. 33.
    Fersht AR. 1995.. Optimization of rates of protein folding: the nucleation-condensation mechanism and its implications. . PNAS 92::10869–73
     [Crossref] [Google Scholar]
  34. 34.
    Fersht AR. 2024.. From covalent transition states in chemistry to noncovalent in biology: from β- to Φ-value analysis of protein folding. . Q. Rev. Biophys. 57::e4
     [Crossref] [Google Scholar]
  35. 35.
    Fleming PJ, Rose GD. 2005.. Do all backbone polar groups in proteins form hydrogen bonds?. Protein Sci. 14::1911–17
     [Crossref] [Google Scholar]
  36. 36.
    Flory PJ. 1969.. Statistical Mechanics of Chain Molecules. New York:: Wiley
     [Google Scholar]
  37. 37.
    Fuentes EJ, Wand AJ. 1998.. Local dynamics and stability of apocytochrome b562 examined by hydrogen exchange. . Biochemistry 37::3687–98
     [Crossref] [Google Scholar]
  38. 38.
    Fuentes EJ, Wand AJ. 1998.. Local stability and dynamics of apocytochrome b562 examined by the dependence of hydrogen exchange on hydrostatic pressure. . Biochemistry 37::9877–83
     [Crossref] [Google Scholar]
  39. 39.
    Fuertes G, Banterle N, Ruff KM, Chowdhury A, Mercadante D, et al. 2017.. Decoupling of size and shape fluctuations in heteropolymeric sequences reconciles discrepancies in SAXS versus FRET measurements. . PNAS 114::242–50
     [Crossref] [Google Scholar]
  40. 40.
    Gates ZP, Baxa MC, Yu W, Riback JA, Li H, et al. 2017.. Perplexing cooperative folding and stability of a low-sequence complexity, polyproline 2 protein lacking a hydrophobic core. . PNAS 114::2241–46
     [Crossref] [Google Scholar]
  41. 41.
    Gazi AD, Bastaki M, Charova SN, Gkougkoulia EA, Kapellios EA, et al. 2008.. Evidence for a coiled-coil interaction mode of disordered proteins from bacterial type III secretion systems. . J. Biol. Chem. 283::34062–68
     [Crossref] [Google Scholar]
  42. 42.
    Gillespie B, Plaxco KW. 2000.. Nonglassy kinetics in the folding of a simple single-domain protein. . PNAS 97::12014–19
     [Crossref] [Google Scholar]
  43. 43.
    Gladwin ST, Evans PA. 1996.. Structure of very early protein folding intermediates: new insights through a variant of hydrogen exchange labelling. . Fold. Des. 1::407–17
     [Crossref] [Google Scholar]
  44. 44.
    Grantcharova VP, Baker D. 1997.. Folding dynamics of the src SH3 domain. . Biochemistry 36::15685–92
     [Crossref] [Google Scholar]
  45. 45.
    Hagen SJ, Eaton WA. 2000.. Two-state expansion and collapse of a polypeptide. . J. Mol. Biol. 297::781–89
     [Crossref] [Google Scholar]
  46. 46.
    Haran G. 2012.. How, when and why proteins collapse: the relation to folding. . Curr. Opin. Struct. Biol. 22::14–20
     [Crossref] [Google Scholar]
  47. 47.
    Harish B, Gillilan RE, Zou J, Wang J, Raleigh DP, Royer CA. 2021.. Protein unfolded states populated at high and ambient pressure are similarly compact. . Biophys. J. 120::2592–98
     [Crossref] [Google Scholar]
  48. 48.
    Holehouse AS, Pappu RV. 2018.. Collapse transitions of proteins and the interplay among backbone, sidechain, and solvent interactions. . Annu. Rev. Biophys. 47::19–39
     [Crossref] [Google Scholar]
  49. 49.
    Huang GS, Oas TG. 1995.. Structure and stability of monomeric lambda repressor: NMR evidence for two-state folding. . Biochemistry 34::3884–92
     [Crossref] [Google Scholar]
  50. 50.
    Huang GS, Oas TG. 1996.. Heat and cold denatured states of monomeric lambda repressor are thermodynamically and conformationally equivalent. . Biochemistry 35::6173–80
     [Crossref] [Google Scholar]
  51. 51.
    Huyghues-Despointes BMP, Scholtz JM, Pace CN. 1999.. Protein conformational stabilities can be determined from hydrogen exchange rates. . Nat. Struct. Biol. 6::910–12 Compares ΔG from HDX and equilibrium experiments after correcting for proline isomerization.
     [Crossref] [Google Scholar]
  52. 52.
    Jackson SE. 1998.. How do small single-domain proteins fold?. Fold. Des. 3::R81–91
     [Crossref] [Google Scholar]
  53. 53.
    Jackson SE, Fersht AR. 1991.. Folding of chymotrypsin inhibitor 2. 1. Evidence for a two-state transition. . Biochemistry 30::10428–35 Chevron analysis demonstrates two-state folding even at 0 M GdmCl; ΔG from kinetic and equilibrium studies match.
     [Crossref] [Google Scholar]
  54. 54.
    Jacob J, Dothager RS, Thiyagarajan P, Sosnick TR. 2007.. Fully reduced ribonuclease A does not expand at high denaturant concentration or temperature. . J. Mol. Biol. 367::609–15
     [Crossref] [Google Scholar]
  55. 55.
    Jacob J, Krantz B, Dothager RS, Thiyagarajan P, Sosnick TR. 2004.. Early collapse is not an obligate step in protein folding. . J. Mol. Biol. 338::369–82
     [Crossref] [Google Scholar]
  56. 56.
    Jha AK, Colubri A, Freed KF, Sosnick TR. 2005.. Statistical coil model of the unfolded state: resolving the reconciliation problem. . PNAS 102::13099–104
     [Crossref] [Google Scholar]
  57. 57.
    Jha AK, Colubri A, Zaman MH, Koide S, Sosnick TR, Freed KF. 2005.. Helix, sheet, and polyproline II frequencies and strong nearest neighbor effects in a restricted coil library. . Biochemistry 44::9691–702
     [Crossref] [Google Scholar]
  58. 58.
    Kathuria SV, Kayatekin C, Barrea R, Kondrashkina E, Graceffa R, et al. 2014.. Microsecond barrier-limited chain collapse observed by time-resolved FRET and SAXS. . J. Mol. Biol. 426::1980–94
     [Crossref] [Google Scholar]
  59. 59.
    Kauzmann W. 1959.. Some factors in interpretation of protein denaturation. . Adv. Prot. Chem. 14::1–63
     [Google Scholar]
  60. 60.
    Kjaergaard M, Norhølm A-B, Hendus-Altenburger R, Pedersen SF, Poulsen FM, Kragelund BB. 2010.. Temperature-dependent structural changes in intrinsically disordered proteins: formation of α-helices or loss of polyproline II?. Protein Sci. 19::1555–64
     [Crossref] [Google Scholar]
  61. 61.
    Kohn JE, Millett IS, Jacob J, Zagrovic B, Dillon TM, et al. 2004.. Random-coil behavior and the dimensions of chemically unfolded proteins. . PNAS 101::12491–96
     [Crossref] [Google Scholar]
  62. 62.
    Kolonko M, Ozga K, Holubowicz R, Taube M, Kozak M, et al. 2016.. Intrinsic disorder of the C-terminal domain of Drosophila methoprene-tolerant protein. . PLOS ONE 11::e0162950
     [Crossref] [Google Scholar]
  63. 63.
    Konno T, Tanaka N, Kataoka M, Takano E, Maki M. 1997.. A circular dichroism study of preferential hydration and alcohol effects on a denatured protein, pig calpastatin domain I. . Biochim. Biophys. Acta 1342::73–82
     [Crossref] [Google Scholar]
  64. 64.
    Krantz BA, Dothager RS, Sosnick TR. 2004.. Discerning the structure and energy of multiple transition states in protein folding using ψ-analysis. . J. Mol. Biol. 337::463–75. Erratum. 2005. . J. Mol. Biol. 347::1103
     [Google Scholar]
  65. 65.
    Krantz BA, Mayne L, Rumbley J, Englander SW, Sosnick TR. 2002.. Fast and slow intermediate accumulation and the initial barrier mechanism in protein folding. . J. Mol. Biol. 324::359–71
     [Crossref] [Google Scholar]
  66. 66.
    Krantz BA, Moran LB, Kentsis A, Sosnick TR. 2000.. D/H amide kinetic isotope effects reveal when hydrogen bonds form during protein folding. . Nat. Struct. Biol. 7::62–71
     [Crossref] [Google Scholar]
  67. 67.
    Krantz BA, Sosnick TR. 2000.. Distinguishing between two-state and three-state models for ubiquitin folding. . Biochemistry 39::11696–701
     [Crossref] [Google Scholar]
  68. 68.
    Krantz BA, Sosnick TR. 2001.. Engineered metal binding sites map the heterogeneous folding landscape of a coiled coil. . Nat. Struct. Biol. 8::1042–47
     [Crossref] [Google Scholar]
  69. 69.
    Krantz BA, Srivastava AK, Nauli S, Baker D, Sauer RT, Sosnick TR. 2002.. Understanding protein hydrogen bond formation with kinetic H/D amide isotope effects. . Nat. Struct. Biol. 9::458–63
     [Crossref] [Google Scholar]
  70. 70.
    Krishna MM, Maity H, Rumbley JN, Lin Y, Englander SW. 2006.. Order of steps in the cytochrome C folding pathway: evidence for a sequential stabilization mechanism. . J. Mol. Biol. 359::1410–19
     [Crossref] [Google Scholar]
  71. 71.
    Lens Z, Dewitte F, Monte D, Baert JL, Bompard C, et al. 2010.. Solution structure of the N-terminal transactivation domain of ERM modified by SUMO-1. . Biochem. Biophys. Res. Commun. 399::104–10
     [Crossref] [Google Scholar]
  72. 72.
    Li Y, Shan B, Raleigh DP. 2007.. The cold denatured state is compact but expands at low temperatures: hydrodynamic properties of the cold denatured state of the C-terminal domain of L9. . J. Mol. Biol. 368::256–62
     [Crossref] [Google Scholar]
  73. 73.
    Luan B, Shan B, Baiz C, Tokmakoff A, Raleigh DP. 2013.. Cooperative cold denaturation: the case of the C-terminal domain of ribosomal protein L9. . Biochemistry 52::2402–9
     [Crossref] [Google Scholar]
  74. 74.
    Makhatadze GI, Privalov PL. 1995.. Energetics of protein structure. . Adv. Protein Chem. 47::307–425
     [Crossref] [Google Scholar]
  75. 75.
    Martin EW, Holehouse AS, Grace CR, Hughes A, Pappu RV, Mittag T. 2016.. Sequence determinants of the conformational properties of an intrinsically disordered protein prior to and upon multisite phosphorylation. . J. Am. Chem. Soc. 138::15323–35
     [Crossref] [Google Scholar]
  76. 76.
    Mayne L, Englander SW. 2000.. Two-state versus multistate protein unfolding studied by optical melting and hydrogen exchange. . Protein Sci. 9::1873–77
     [Crossref] [Google Scholar]
  77. 77.
    Meisner WK, Sosnick TR. 2004.. Barrier-limited, microsecond folding of a stable protein measured with hydrogen exchange: implications for downhill folding. . PNAS 101::15639–44
     [Crossref] [Google Scholar]
  78. 78.
    Moncoq K, Broutin I, Craescu CT, Vachette P, Ducruix A, Durand D. 2004.. SAXS study of the PIR domain from the Grb14 molecular adaptor: a natively unfolded protein with a transient structure primer?. Biophys. J. 87::4056–64
     [Crossref] [Google Scholar]
  79. 79.
    Murphy KP, Freire E. 1992.. Thermodynamics of structural stability and cooperative folding behavior in proteins. . Adv. Protein Chem. 43::313–61
     [Crossref] [Google Scholar]
  80. 80.
    Myers JK, Pace CN, Scholtz JM. 1995.. Denaturant m values and heat capacity changes: relation to changes in accessible surface areas of protein unfolding. . Protein Sci. 4::2138–48
     [Crossref] [Google Scholar]
  81. 81.
    Naganathan AN, Muñoz V. 2010.. Insights into protein folding mechanisms from large scale analysis of mutational effects. . PNAS 107::8611–16
     [Crossref] [Google Scholar]
  82. 82.
    Narayan A, Bhattacharjee K, Naganathan AN. 2019.. Thermally versus chemically denatured protein states. . Biochemistry 58::2519–23
     [Crossref] [Google Scholar]
  83. 83.
    Nath U, Udgaonkar JB. 1997.. Folding of tryptophan mutants of barstar: evidence for an initial hydrophobic collapse on the folding pathway. . Biochemistry 36::8602–10
     [Crossref] [Google Scholar]
  84. 84.
    Nöppert A, Gast K, Müller-Frohne M, Zirwer D, Damaschun G. 1996.. Reduced-denatured ribonuclease A is not in a compact state. . FEBS Lett. 380::179–82
     [Crossref] [Google Scholar]
  85. 85.
    Pace CN, Shirley BA, McNutt M, Gajiwala K. 1996.. Forces contributing to the conformational stability of proteins. . FASEB J. 10::75–83
     [Crossref] [Google Scholar]
  86. 86.
    Pandit AD, Jha A, Freed KF, Sosnick TR. 2006.. Small proteins fold through transition states with native-like topologies. . J. Mol. Biol. 361::755–70
     [Crossref] [Google Scholar]
  87. 87.
    Peran I, Holehouse AS, Carrico IS, Pappu RV, Bilsel O, Raleigh DP. 2019.. Unfolded states under folding conditions accommodate sequence-specific conformational preferences with random coil-like dimensions. . PNAS 116::12301–10
     [Crossref] [Google Scholar]
  88. 88.
    Plaxco KW, Millett IS, Segel DJ, Doniach S, Baker D. 1999.. Chain collapse can occur concomitantly with the rate-limiting step in protein folding. . Nat. Struct. Biol. 6::554–56
     [Crossref] [Google Scholar]
  89. 89.
    Plaxco KW, Simons KT, Baker D. 1998.. Contact order, transition state placement and the refolding rates of single domain proteins. . J. Mol. Biol. 277::985–94
     [Crossref] [Google Scholar]
  90. 90.
    Porter LL, Rose GD. 2011.. Redrawing the Ramachandran plot after inclusion of hydrogen-bonding constraints. . PNAS 108::109–13
     [Crossref] [Google Scholar]
  91. 91.
    Privalov PL. 1989.. Thermodynamic problems of protein structure. . Annu. Rev. Biophys. Biophys. Chem. 18::47–69
     [Crossref] [Google Scholar]
  92. 92.
    Privalov PL. 1990.. Cold denaturation of proteins. . Crit. Rev. Biochem. Mol. Biol. 25::281–305
     [Crossref] [Google Scholar]
  93. 93.
    Qi PX, Sosnick TR, Englander SW. 1998.. The burst phase in ribonuclease A folding and solvent dependence of the unfolded state. . Nat. Struct. Biol. 5::882–84
     [Crossref] [Google Scholar]
  94. 94.
    Qu S, Liu C, Liu Q, Wu W, Du B, Wang J. 2018.. Solvent effect on FRET spectroscopic ruler. . J. Chem. Phys. 148::123331
     [Crossref] [Google Scholar]
  95. 95.
    Reddy G, Thirumalai D. 2017.. Collapse precedes folding in denaturant-dependent assembly of ubiquitin. . J. Phys. Chem. B 121::995–1009
     [Crossref] [Google Scholar]
  96. 96.
    Renner M, Paesen GC, Grison CM, Granier S, Grimes JM, Leyrat C. 2017.. Structural dissection of human metapneumovirus phosphoprotein using small angle X-ray scattering. . Sci. Rep. 7::14865
     [Crossref] [Google Scholar]
  97. 97.
    Riback JA, Bowman MA, Zmyslowski AM, Knoverek CR, Jumper JM, et al. 2017.. Innovative scattering analysis shows that hydrophobic disordered proteins are expanded in water. . Science 358::238–41 Development of the molecular form factor for extracting Rg and ν from SAXS experiments.
     [Crossref] [Google Scholar]
  98. 98.
    Riback JA, Bowman MA, Zmyslowski A, Knoverek CR, Jumper J, et al. 2018.. Response to Comment on “Innovative scattering analysis shows that hydrophobic disordered proteins are expanded in water. .” Science 361::eaar7949
     [Crossref] [Google Scholar]
  99. 99.
    Riback JA, Bowman MA, Zmyslowski AM, Plaxco KW, Clark PL, Sosnick TR. 2019.. Commonly used FRET fluorophores promote collapse of an otherwise disordered protein. . PNAS 116::8889–94
     [Crossref] [Google Scholar]
  100. 100.
    Roche J, Royer CA. 2018.. Lessons from pressure denaturation of proteins. . J. R. Soc. Interface 15::20180244
     [Crossref] [Google Scholar]
  101. 101.
    Rose GD. 2021.. Reframing the protein folding problem: entropy as organizer. . Biochemistry 60::3753–61
     [Crossref] [Google Scholar]
  102. 102.
    Sadqi M, Lapidus LJ, Muñoz V. 2003.. How fast is protein hydrophobic collapse?. PNAS 100::12117–22
     [Crossref] [Google Scholar]
  103. 103.
    Schwartz R, King J. 2006.. Frequencies of hydrophobic and hydrophilic runs and alternations in proteins of known structure. . Protein Sci. 15::102–12
     [Crossref] [Google Scholar]
  104. 104.
    Shell SS, Putnam CD, Kolodner RD. 2007.. The N terminus of Saccharomyces cerevisiae Msh6 is an unstructured tether to PCNA. . Mol. Cell 26::565–78
     [Crossref] [Google Scholar]
  105. 105.
    Skinner JJ, Yu W, Gichana EK, Baxa MC, Hinshaw JR, et al. 2014.. Benchmarking all-atom simulations using hydrogen exchange. . PNAS 111::15975–80
     [Crossref] [Google Scholar]
  106. 106.
    Sosnick TR, Dothager RS, Krantz BA. 2004.. Differences in the folding transition state of ubiquitin indicated by ϕ and ψ analyses. . PNAS 101::17377–82
     [Crossref] [Google Scholar]
  107. 107.
    Sosnick TR, Krantz BA, Dothager RS, Baxa M. 2006.. Characterizing the protein folding transition state using ψ analysis. . Chem. Rev. 106::1862–76
     [Crossref] [Google Scholar]
  108. 108.
    Sosnick TR, Mayne L, Englander SW. 1996.. Molecular collapse: the rate-limiting step in two-state cytochrome c folding. . Proteins 24::413–26
     [Crossref] [Google Scholar]
  109. 109.
    Sosnick TR, Mayne L, Hiller R, Englander SW. 1994.. The barriers in protein folding. . Nat. Struct. Biol. 1::149–56
     [Crossref] [Google Scholar]
  110. 110.
    Sosnick TR, Shtilerman MD, Mayne L, Englander SW. 1997.. Ultrafast signals in protein folding and the polypeptide contracted state. . PNAS 94::8545–50
     [Crossref] [Google Scholar]
  111. 111.
    Sosnick TR, Trewhella J. 1992.. Denatured states of ribonuclease A have compact dimensions and residual secondary structure. . Biochemistry 31::8329–35
     [Crossref] [Google Scholar]
  112. 112.
    Stenzoski NE, Luan B, Holehouse AS, Raleigh DP. 2018.. The unfolded state of the C-terminal domain of L9 expands at low but not at elevated temperatures. . Biophys. J. 115::655–63
     [Crossref] [Google Scholar]
  113. 113.
    Tischer A, Machha VR, Rösgen J, Auton M. 2018.. “ Cooperative collapse” of the denatured state revealed through Clausius-Clapeyron analysis of protein denaturation phase diagrams. . Biopolymers 109::e23106
     [Crossref] [Google Scholar]
  114. 114.
    Toal S, Schweitzer-Stenner R. 2014.. Local order in the unfolded state: conformational biases and nearest neighbor interactions. . Biomolecules 4::725–73
     [Crossref] [Google Scholar]
  115. 115.
    Wang Y, Trewhella J, Goldenberg DP. 2008.. Small-angle X-ray scattering of reduced ribonuclease A: effects of solution conditions and comparisons with a computational model of unfolded proteins. . J. Mol. Biol. 377::1576–92
     [Crossref] [Google Scholar]
  116. 116.
    Watkins HM, Simon AJ, Sosnick TR, Lipman EA, Hjelm RP, Plaxco KW. 2015.. Random coil negative control reproduces the discrepancy between scattering and FRET measurements of denatured protein dimensions. . PNAS 112::6631–36
     [Crossref] [Google Scholar]
  117. 117.
    Watson MC, Curtis JE. 2014.. Probing the average local structure of biomolecules using small-angle scattering and scaling laws. . Biophys. J. 106::2474–82
     [Crossref] [Google Scholar]
  118. 118.
    Wells M, Tidow H, Rutherford TJ, Markwick P, Jensen MR, et al. 2008.. Structure of tumor suppressor p53 and its intrinsically disordered N-terminal transactivation domain. . PNAS 105::5762–67
     [Crossref] [Google Scholar]
  119. 119.
    Whitten ST, Kurtz AJ, Pometun MS, Wand AJ, Hilser VJ. 2006.. Revealing the nature of the native state ensemble through cold denaturation. . Biochemistry 45::10163–74
     [Crossref] [Google Scholar]
  120. 120.
    Wu Y, Kondrashkina E, Kayatekin C, Matthews CR, Bilsel O. 2008.. Microsecond acquisition of heterogeneous structure in the folding of a TIM barrel protein. . PNAS 105::13367–72
     [Crossref] [Google Scholar]
  121. 121.
    Wuttke R, Hofmann H, Nettels D, Borgia MB, Mittal J, et al. 2014.. Temperature-dependent solvation modulates the dimensions of disordered proteins. . PNAS 111::5213–18
     [Crossref] [Google Scholar]
  122. 122.
    Yang C, van der Woerd MJ, Muthurajan UM, Hansen JC, Luger K. 2011.. Biophysical analysis and small-angle X-ray scattering-derived structures of MeCP2-nucleosome complexes. . Nucleic Acids Res. 39::4122–35
     [Crossref] [Google Scholar]
  123. 123.
    Yoo TY, Meisburger SP, Hinshaw J, Pollack L, Haran G, et al. 2012.. Small-angle X-ray scattering and single-molecule FRET spectroscopy produce highly divergent views of the low-denaturant unfolded state. . J. Mol. Biol. 418::226–36
     [Crossref] [Google Scholar]
  124. 124.
    Yu W, Baxa MC, Gagnon I, Freed KF, Sosnick TR. 2016.. Cooperative folding near the downhill limit determined with amino acid resolution by hydrogen exchange. . PNAS 113::4747–52
     [Crossref] [Google Scholar]
  125. 125.
    Zheng Z, Sosnick TR. 2010.. Protein vivisection reveals elusive intermediates in folding. . J. Mol. Biol. 397::777–88
     [Crossref] [Google Scholar]
/content/journals/10.1146/annurev-biophys-080124-123012
Loading
Collapse and Protein Folding: Should We Be Surprised That Biothermodynamics Works So Well?
Annual Review of Biophysics 54, 17 (2025); https://doi.org/10.1146/annurev-biophys-080124-123012
/content/journals/10.1146/annurev-biophys-080124-123012
/content/journals/10.1146/annurev-biophys-080124-123012
Loading

Data & Media loading...

Most Cited Most Cited RSS feed

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error