1932

Abstract

Proteins can collapse into compact globules or form expanded, solvent-accessible, coil-like conformations. Additionally, they can fold into well-defined three-dimensional structures or remain partially or entirely disordered. Recent discoveries have shown that the tendency for proteins to collapse or remain expanded is not intrinsically coupled to their ability to fold. These observations suggest that proteins do not have to form compact globules in aqueous solutions. They can be intrinsically disordered, collapsed, or expanded, and even form well-folded, elongated structures. This ability to decouple collapse from folding is determined by the sequence details of proteins. In this review, we highlight insights gleaned from studies over the past decade. Using a polymer physics framework, we explain how the interplay among sidechains, backbone units, and solvent determines the driving forces for collapsed versus expanded states in aqueous solvents.

Loading

Article metrics loading...

/content/journals/10.1146/annurev-biophys-070317-032838
2018-05-20
2024-03-28
Loading full text...

Full text loading...

/deliver/fulltext/biophys/47/1/annurev-biophys-070317-032838.html?itemId=/content/journals/10.1146/annurev-biophys-070317-032838&mimeType=html&fmt=ahah

Literature Cited

  1. 1.  Aksel T, Majumdar A, Barrick D 2011. The contribution of entropy, enthalpy, and hydrophobic desolvation to cooperativity in repeat-protein folding. Structure 19:349–60
    [Google Scholar]
  2. 2.  Asthagiri D, Karandur D, Tomar DS, Pettitt BM 2017. Intramolecular interactions overcome hydration to drive the collapse transition of Gly15. J. Phys. Chem. B 121:8078–84
    [Google Scholar]
  3. 3.  Auton M, Holthauzen LMF, Bolen DW 2007. Anatomy of energetic changes accompanying urea-induced protein denaturation. PNAS 104:15317–22
    [Google Scholar]
  4. 4.  Aznauryan M, Delgado L, Soranno A, Nettels D, Huang J-R et al. 2016. Comprehensive structural and dynamical view of an unfolded protein from the combination of single-molecule FRET, NMR, and SAXS. PNAS 113:E5389–98
    [Google Scholar]
  5. 5.  Bah A, Vernon RM, Siddiqui Z, Krzeminski M, Muhandiram R et al. 2015. Folding of an intrinsically disordered protein by phosphorylation as a regulatory switch. Nature 519:106–9
    [Google Scholar]
  6. 6.  Baker EG, Bartlett GJ, Crump MP, Sessions RB, Linden N et al. 2015. Local and macroscopic electrostatic interactions in single α-helices. Nat. Chem. Biol. 11:221–28
    [Google Scholar]
  7. 7.  Baldwin RL, Frieden C, Rose GD 2010. Dry molten globule intermediates and the mechanism of protein unfolding. Proteins 78:2725–37
    [Google Scholar]
  8. 8.  Banani SF, Lee HO, Hyman AA, Rosen MK 2017. Biomolecular condensates: organizers of cellular biochemistry. Nat. Rev. Mol. Cell Biol. 18:285–98
    [Google Scholar]
  9. 9.  Banavar JR, Maritan A 2007. Physics of proteins. Annu. Rev. Biophys. Biomol. Struct. 36:261–80
    [Google Scholar]
  10. 10.  Ben-Naim A. 2013. Solvation Thermodynamics New York: Springer Sci. Bus. Media
  11. 11.  Berisio R, Vitagliano L, Mazzarella L, Zagari A 2002. Crystal structure of the collagen triple helix model [(Pro-Pro-Gly)10]3. Protein Sci 11:262–70
    [Google Scholar]
  12. 12.  Best RB, Zheng W, Mittal J 2014. Balanced protein–water interactions improve properties of disordered proteins and non-specific protein association. J. Chem. Theory Comput. 10:5113–24
    [Google Scholar]
  13. 13.  Bloom JD, Labthavikul ST, Otey CR, Arnold FH 2006. Protein stability promotes evolvability. PNAS 103:5869–74
    [Google Scholar]
  14. 14.  Bolen DW, Rose GD 2008. Structure and energetics of the hydrogen-bonded backbone in protein folding. Annu. Rev. Biochem. 77:339–62
    [Google Scholar]
  15. 15.  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
    [Google Scholar]
  16. 16.  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
    [Google Scholar]
  17. 17.  Camacho CJ, Thirumalai D 1993. Kinetics and thermodynamics of folding in model proteins. PNAS 90:6369–72
    [Google Scholar]
  18. 18.  Canchi DR, García AE 2013. Cosolvent effects on protein stability. Annu. Rev. Phys. Chem. 64:273–93
    [Google Scholar]
  19. 19.  Capraro DT, Roy M, Onuchic JN, Jennings PA 2008. Backtracking on the folding landscape of the β-trefoil protein interleukin-1β. ? PNAS 105:14844–48
    [Google Scholar]
  20. 20.  Chan HS, Dill KA 1991. Polymer principles in protein structure and stability. Annu. Rev. Biophys. Biophys. Chem. 20:447–90
    [Google Scholar]
  21. 21.  Cho J-H, Meng W, Sato S, Kim EY, Schindelin H, Raleigh DP 2014. Energetically significant networks of coupled interactions within an unfolded protein. PNAS 111:12079–84
    [Google Scholar]
  22. 22.  Cho J-H, Sato S, Raleigh DP 2004. Thermodynamics and kinetics of non-native interactions in protein folding: a single point mutant significantly stabilizes the N-terminal domain of L9 by modulating non-native interactions in the denatured state. J. Mol. Biol. 338:827–37
    [Google Scholar]
  23. 23.  Chong PA, Ozdamar B, Wrana JL, Forman-Kay JD 2004. Disorder in a target for the Smad2 Mad homology 2 domain and its implications for binding and specificity. J. Biol. Chem. 279:40707–14
    [Google Scholar]
  24. 24.  Choy W-Y, Mulder FAA, Crowhurst KA, Muhandiram DR, Millett IS et al. 2002. Distribution of molecular size within an unfolded state ensemble using small-angle X-ray scattering and pulse field gradient NMR techniques. J. Mol. Biol. 316:101–12
    [Google Scholar]
  25. 25.  Crick SL, Jayaraman M, Frieden C, Wetzel R, Pappu RV 2006. Fluorescence correlation spectroscopy shows that monomeric polyglutamine molecules form collapsed structures in aqueous solutions. PNAS 103:16764–69
    [Google Scholar]
  26. 26.  Crowhurst KA, Forman-Kay JD 2003. Aromatic and methyl NOEs highlight hydrophobic clustering in the unfolded state of an SH3 domain. Biochemistry 42:8687–95
    [Google Scholar]
  27. 27.  Das RK, Huang Y, Phillips AH, Kriwacki RW, Pappu RV 2016. Cryptic sequence features within the disordered protein p27Kip1 regulate cell cycle signaling. PNAS 113:5616–21
    [Google Scholar]
  28. 28.  Das RK, Pappu RV 2013. Conformations of intrinsically disordered proteins are influenced by linear sequence distributions of oppositely charged residues. PNAS 110:13392–97
    [Google Scholar]
  29. 29.  Das RK, Ruff KM, Pappu RV 2015. Relating sequence encoded information to form and function of intrinsically disordered proteins. Curr. Opin. Struct. Biol. 32:102–12
    [Google Scholar]
  30. 30.  Davis CM, Gruebele M, Sukenik S 2017. How does solvation in the cell affect protein folding and binding?. Curr. Opin. Struct. Biol. 48:23–29
    [Google Scholar]
  31. 31.  de Gennes PG 1975. Collapse of a polymer chain in poor solvents. J. Phys. Lett. 36:55–57
    [Google Scholar]
  32. 32.  de Gennes PG 1979. Scaling Concepts in Polymer Physics Ithaca, NY: Cornell Univ. Press
  33. 33.  Dill KA. 1990. Dominant forces in protein folding. Biochemistry 29:7133–55
    [Google Scholar]
  34. 34.  Dill KA, Shortle D 1991. Denatured states of proteins. Annu. Rev. Biochem. 60:795–825
    [Google Scholar]
  35. 35.  Dima RI, Thirumalai D 2004. Asymmetry in the shapes of folded and denatured states of proteins. J. Phys. Chem. B 108:6564–70
    [Google Scholar]
  36. 36.  Edwards SF. 1967. Statistical mechanics with topological constraints: I. Proc. Phys. Soc. Lond. 91:513
    [Google Scholar]
  37. 37.  Englander SW. 2000. Protein folding intermediates and pathways studied by hydrogen exchange. Annu. Rev. Biophys. Biomol. Struct. 29:213–38
    [Google Scholar]
  38. 38.  Englander SW, Mayne L 2014. The nature of protein folding pathways. PNAS 111:15873–80
    [Google Scholar]
  39. 39.  Fink AL, Calciano LJ, Goto Y, Kurotsu T, Palleros DR 1994. Classification of acid denaturation of proteins: intermediates and unfolded states. Biochemistry 33:12504–11
    [Google Scholar]
  40. 40.  Finkelstein AV, Shakhnovich EI 1989. Theory of cooperative transitions in protein molecules. II. Phase diagram for a protein molecule in solution. Biopolymers 28:1681–94
    [Google Scholar]
  41. 41.  Flory PJ. 1953. Principles of Polymer Chemistry Ithaca, NY: Cornell Univ. Press
  42. 42.  Flory PJ. 1969. Statistical Mechanics of Chain Molecules New York: Oxford Univ. Press
  43. 43.  Fossat MJ, Dao TP, Jenkins K, Dellarole M, Yang Y et al. 2016. High-resolution mapping of a repeat protein folding free energy landscape. Biophys. J. 111:2368–76
    [Google Scholar]
  44. 44.  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 vs. FRET measurements. PNAS 114:E6342–51
    [Google Scholar]
  45. 45.  Gangadhara BN, Laine JM, Kathuria SV, Massi F, Matthews CR 2013. Clusters of branched aliphatic side chains serve as cores of stability in the native state of the HisF TIM barrel protein. J. Mol. Biol. 425:1065–81
    [Google Scholar]
  46. 46.  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
    [Google Scholar]
  47. 47.  Gibbs EB, Lu F, Portz B, Fisher MJ, Medellin BP et al. 2017. Phosphorylation induces sequence-specific conformational switches in the RNA polymerase II C-terminal domain. Nat. Commun. 8:15233
    [Google Scholar]
  48. 48.  Goldenberg DP. 2003. Computational simulation of the statistical properties of unfolded proteins. J. Mol. Biol. 326:1615–33
    [Google Scholar]
  49. 49.  Goluguri RR, Udgaonkar JB 2016. Microsecond rearrangements of hydrophobic clusters in an initially collapsed globule prime structure formation during the folding of a small protein. J. Mol. Biol. 428:3102–17
    [Google Scholar]
  50. 50.  Griep S, Hobohm U 2010. PDBselect 1992–2009 and PDBfilter-select. Nucleic Acids Res 38:D318–19
    [Google Scholar]
  51. 51.  Grosberg AY, Kuznetsov DV 1992. Quantitative theory of the globule-to-coil transition. 1. Link density distribution in a globule and its radius of gyration. Macromolecules 25:1970–79
    [Google Scholar]
  52. 52.  Gruszka DT, Wojdyla JA, Bingham RJ, Turkenburg JP, Manfield IW et al. 2012. Staphylococcal biofilm-forming protein has a contiguous rod-like structure. PNAS 109:E1011–18
    [Google Scholar]
  53. 53.  Guinn EJ, Jagannathan B, Marqusee S 2015. Single-molecule chemo-mechanical unfolding reveals multiple transition state barriers in a small single-domain protein. Nat. Commun. 6:6861
    [Google Scholar]
  54. 54.  Harmon TS, Holehouse AS, Rosen MK, Pappu RV 2017. Intrinsically disordered linkers determine the interplay between phase separation and gelation in multivalent proteins. eLife 6:e30294.
  55. 55.  Higgs PG, Joanny J-F 1991. Theory of polyampholyte solutions. J. Chem. Phys. 94:1543–54
    [Google Scholar]
  56. 56.  Hodsdon ME, Frieden C 2001. Intestinal fatty acid binding protein: the folding mechanism as determined by NMR studies. Biochemistry 40:732–42
    [Google Scholar]
  57. 57.  Hofmann H, Soranno A, Borgia A, Gast K, Nettels D, Schuler B 2012. Polymer scaling laws of unfolded and intrinsically disordered proteins quantified with single-molecule spectroscopy. PNAS 109:16155–60
    [Google Scholar]
  58. 58.  Holehouse AS, Das RK, Ahad JN, Richardson MOG, Pappu RV 2017. CIDER: resources to analyze sequence-ensemble relationships of intrinsically disordered proteins. Biophys. J. 112:16–21
    [Google Scholar]
  59. 59.  Holehouse AS, Garai K, Lyle N, Vitalis A, Pappu RV 2015. Quantitative assessments of the distinct contributions of polypeptide backbone amides versus side chain groups to chain expansion via chemical denaturation. J. Am. Chem. Soc. 137:2984–95
    [Google Scholar]
  60. 60.  Hu W, Walters BT, Kan Z-Y, Mayne L, Rosen LE et al. 2013. Stepwise protein folding at near amino acid resolution by hydrogen exchange and mass spectrometry. PNAS 110:7684–89
    [Google Scholar]
  61. 61.  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
    [Google Scholar]
  62. 62.  Jain N, Bhattacharya M, Mukhopadhyay S 2011. Chain collapse of an amyloidogenic intrinsically disordered protein. Biophys. J. 101:1720–29
    [Google Scholar]
  63. 63.  Jha SK, Marqusee S 2014. Kinetic evidence for a two-stage mechanism of protein denaturation by guanidinium chloride. PNAS 111:4856–61
    [Google Scholar]
  64. 64.  Kang H, Vázquez FX, Zhang L, Das P, Toledo-Sherman L et al. 2017. Emerging β-sheet rich conformations in supercompact Huntingtin exon-1 mutant structures. J. Am. Chem. Soc. 139:8820–27
    [Google Scholar]
  65. 65.  Karandur D, Harris RC, Pettitt BM 2016. Protein collapse driven against solvation free energy without H-bonds. Protein Sci 25:103–10
    [Google Scholar]
  66. 66.  Karandur D, Wong K-Y, Pettitt BM 2014. Solubility and aggregation of Gly5 in water. J. Phys. Chem. B 118:9565–72
    [Google Scholar]
  67. 67.  Kathuria SV, Chan YH, Nobrega RP, Özen A, Matthews CR 2016. Clusters of isoleucine, leucine, and valine side chains define cores of stability in high-energy states of globular proteins: sequence determinants of structure and stability. Protein Sci 25:662–75
    [Google Scholar]
  68. 68.  Kimura T, Uzawa T, Ishimori K, Morishima I, Takahashi S et al. 2005. Specific collapse followed by slow hydrogen-bond formation of β-sheet in the folding of single-chain monellin. PNAS 102:2748–53
    [Google Scholar]
  69. 69.  Klein-Seetharaman J, Oikawa M, Grimshaw SB, Wirmer J, Duchardt E et al. 2002. Long-range interactions within a nonnative protein. Science 295:1719–22
    [Google Scholar]
  70. 70.  Klimov DK, Thirumalai D 1996. Criterion that determines the foldability of proteins. Phys. Rev. Lett. 76:4070–73
    [Google Scholar]
  71. 71.  Klimov DK, Thirumalai D 1996. Factors governing the foldability of proteins. Proteins 26:411–41
    [Google Scholar]
  72. 72.  Kobe B, Kajava AV 2001. The leucine-rich repeat as a protein recognition motif. Curr. Opin. Struct. Biol. 11:725–32
    [Google Scholar]
  73. 73.  Kohl A, Binz HK, Forrer P, Stumpp MT, Plückthun A, Grütter MG 2003. Designed to be stable: crystal structure of a consensus ankyrin repeat protein. PNAS 100:1700–5
    [Google Scholar]
  74. 74.  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
    [Google Scholar]
  75. 75.  Kutyshenko VP, Prokhorov DA, Mikoulinskaia GV, Molochkov NV, Paskevich SI, Uversky VN 2017. Evidence for the residual tertiary structure in the urea-unfolded form of bacteriophage T5 endolysin. J. Biomol. Struct. Dyn. 35:1331–38
    [Google Scholar]
  76. 76.  Li MS, Klimov DK, Thirumalai D 2004. Finite size effects on thermal denaturation of globular proteins. Phys. Rev. Lett. 93:268107
    [Google Scholar]
  77. 77.  Lietzow MA, Jamin M, Dyson HJ, Wright PE 2002. Mapping long-range contacts in a highly unfolded protein. J. Mol. Biol. 322:655–62
    [Google Scholar]
  78. 78.  Lifshitz IM, Grosberg AY, Khokhlov RA 1978. Some problems of the statistical physics of polymer chains with volume interaction. Rev. Mod. Phys. 50:683–713
    [Google Scholar]
  79. 79.  Lim WK, Rösgen J, Englander SW 2009. Urea, but not guanidinium, destabilizes proteins by forming hydrogen bonds to the peptide group. PNAS 106:2595–600
    [Google Scholar]
  80. 80.  Lin Y-H, Song J, Forman-Kay JD, Chan HS 2016. Random-phase-approximation theory for sequence-dependent, biologically functional liquid-liquid phase separation of intrinsically disordered proteins. J. Mol. Liq. 228:176–93
    [Google Scholar]
  81. 81.  Lu X, Murphy RM 2015. Asparagine repeat peptides: aggregation kinetics and comparison with glutamine repeats. Biochemistry 54:4784–94
    [Google Scholar]
  82. 82.  Lupas AN, Bassler J, Dunin-Horkawicz S 2017. The structure and topology of α-helical coiled coils. Subcell. Biochem. 82:95–129
    [Google Scholar]
  83. 83.  Lyle N, Das RK, Pappu RV 2013. A quantitative measure for protein conformational heterogeneity. J. Chem. Phys. 139:121907
    [Google Scholar]
  84. 84.  Maity H, Reddy G 2016. Folding of Protein L with implications for collapse in the denatured state ensemble. J. Am. Chem. Soc. 138:2609–16
    [Google Scholar]
  85. 85.  Mallamace F, Corsaro C, Mallamace D, Vasi S, Vasi C et al. 2016. Energy landscape in protein folding and unfolding. PNAS 113:3159–63
    [Google Scholar]
  86. 86.  Mao AH, Crick SL, Vitalis A, Chicoine CL, Pappu RV 2010. Net charge per residue modulates conformational ensembles of intrinsically disordered proteins. PNAS 107:8183–88
    [Google Scholar]
  87. 87.  Mao AH, Lyle N, Pappu RV 2013. Describing sequence–ensemble relationships for intrinsically disordered proteins. Biochem. J. 449:307–18
    [Google Scholar]
  88. 88.  Marsh JA, Forman-Kay JD 2010. Sequence determinants of compaction in intrinsically disordered proteins. Biophys. J. 98:2383–90
    [Google Scholar]
  89. 89.  Marsh JA, Neale C, Jack FE, Choy W-Y, Lee AY et al. 2007. Improved structural characterizations of the drkN SH3 domain unfolded state suggest a compact ensemble with native-like and non-native structure. J. Mol. Biol. 367:1494–510
    [Google Scholar]
  90. 90.  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
    [Google Scholar]
  91. 91.  Mayor U, Grossmann JG, Foster NW, Freund SMV, Fersht AR 2003. The denatured state of Engrailed Homeodomain under denaturing and native conditions. J. Mol. Biol. 333:977–91
    [Google Scholar]
  92. 92.  Meng W, Luan B, Lyle N, Pappu RV, Raleigh DP 2013. The denatured state ensemble contains significant local and long-range structure under native conditions: analysis of the N-terminal domain of ribosomal protein L9. Biochemistry 52:2662–71
    [Google Scholar]
  93. 93.  Moeser B, Horinek D 2014. Unified description of urea denaturation: backbone and side chains contribute equally in the transfer model. J. Phys. Chem. B 118:107–14
    [Google Scholar]
  94. 94.  Mok KH, Kuhn LT, Goez M, Day IJ, Lin JC et al. 2007. A pre-existing hydrophobic collapse in the unfolded state of an ultrafast folding protein. Nature 447:106–9
    [Google Scholar]
  95. 95.  Mok YK, Kay CM, Kay LE, Forman-Kay J 1999. NOE data demonstrating a compact unfolded state for an SH3 domain under non-denaturing conditions. J. Mol. Biol. 289:619–38
    [Google Scholar]
  96. 96.  Molliex A, Temirov J, Lee J, Coughlin M, Kanagaraj AP et al. 2015. Phase separation by low complexity domains promotes stress granule assembly and drives pathological fibrillization. Cell 163:123–33
    [Google Scholar]
  97. 97.  Mountain RD, Thirumalai D 2003. Molecular dynamics simulations of end-to-end contact formation in hydrocarbon chains in water and aqueous urea solution. J. Am. Chem. Soc. 125:1950–57
    [Google Scholar]
  98. 98.  Mukhopadhyay S, Krishnan R, Lemke EA, Lindquist S, Deniz AA 2007. A natively unfolded yeast prion monomer adopts an ensemble of collapsed and rapidly fluctuating structures. PNAS 104:2649–54
    [Google Scholar]
  99. 99.  Müller-Späth S, Soranno A, Hirschfeld V, Hofmann H, Rüegger S et al. 2010. Charge interactions can dominate the dimensions of intrinsically disordered proteins. PNAS 107:14609–14
    [Google Scholar]
  100. 100.  Neumaier S, Kiefhaber T 2014. Redefining the dry molten globule state of proteins. J. Mol. Biol. 426:2520–28
    [Google Scholar]
  101. 101.  Nobrega RP, Arora K, Kathuria SV, Graceffa R, Barrea RA et al. 2014. Modulation of frustration in folding by sequence permutation. PNAS 111:10562–67
    [Google Scholar]
  102. 102.  Nott TJ, Petsalaki E, Farber P, Jervis D, Fussner E et al. 2015. Phase transition of a disordered nuage protein generates environmentally responsive membraneless organelles. Mol. Cell 57:936–47
    [Google Scholar]
  103. 103.  Outer P, Carr CI, Zimm BH 1950. Light scattering investigation of the structure of polystyrene. J. Chem. Phys. 18:830–39
    [Google Scholar]
  104. 104.  Pace CN, Shaw KL 2000. Linear extrapolation method of analyzing solvent denaturation curves. Proteins 41:Suppl. 41–7
    [Google Scholar]
  105. 105.  Pande VS, Grosberg AY, Tanaka T 2000. Heteropolymer freezing and design: towards physical models of protein folding. Rev. Mod. Phys. 72:259–314
    [Google Scholar]
  106. 106.  Patel A, Lee HO, Jawerth L, Maharana S, Jahnel M et al. 2015. A liquid-to-solid phase transition of the ALS protein FUS accelerated by disease mutation. Cell 162:1066–77
    [Google Scholar]
  107. 107.  Piana S, Klepeis JL, Shaw DE 2014. Assessing the accuracy of physical models used in protein-folding simulations: quantitative evidence from long molecular dynamics simulations. Curr. Opin. Struct. Biol. 24:98–105
    [Google Scholar]
  108. 108.  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
    [Google Scholar]
  109. 109.  Portz B, Lu F, Gibbs EB, Mayfield JE, Mehaffey MR et al. 2017. Structural heterogeneity in the intrinsically disordered RNA polymerase II C-terminal domain. Nat. Commun. 8:15231
    [Google Scholar]
  110. 110.  Ptitsyn OB, Uversky VN 1994. The molten globule is a third thermodynamical state of protein molecules. FEBS Lett 341:15–18
    [Google Scholar]
  111. 111.  Record MT Jr., Guinn E, Pegram L, Capp M. 2013. Introductory lecture: interpreting and predicting Hofmeister salt ion and solute effects on biopolymer and model processes using the solute partitioning model. Faraday Discuss 160:9–44
    [Google Scholar]
  112. 112.  Reddy G, Thirumalai D 2017. Collapse precedes folding in denaturant-dependent assembly of ubiquitin. J. Phys. Chem. B 121:995–1009
    [Google Scholar]
  113. 113.  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
    [Google Scholar]
  114. 114.  Riback JA, Katanski CD, Kear-Scott JL, Pilipenko EV, Rojek AE et al. 2017. Stress-triggered phase separation is an adaptive, evolutionarily tuned response. Cell 168:1028–40.e19
    [Google Scholar]
  115. 115.  Rose GD, Fleming PJ, Banavar JR, Maritan A 2006. A backbone-based theory of protein folding. PNAS 103:16623–33
    [Google Scholar]
  116. 116.  Rubinstein M, Colby RH 2003. Polymer Physics New York: Oxford Univ. Press
  117. 117.  Ruff KM, Holehouse AS 2017. SAXS versus FRET: a matter of heterogeneity. ? Biophys. J. 113:971–73
    [Google Scholar]
  118. 118.  Samanta HS, Zhuravlev PI, Hinczewski M, Hori N, Chakrabarti S, Thirumalai D 2017. Protein collapse is encoded in the folded state architecture. Soft Matter 13:3622–38
    [Google Scholar]
  119. 119.  Sarkar SS, Udgaonkar JB, Krishnamoorthy G 2013. Unfolding of a small protein proceeds via dry and wet globules and a solvated transition state. Biophys. J. 105:2392–402
    [Google Scholar]
  120. 120.  Sawle L, Ghosh K 2015. A theoretical method to compute sequence dependent configurational properties in charged polymers and proteins. J. Chem. Phys. 143:085101
    [Google Scholar]
  121. 121.  Schuler B, Lipman EA, Eaton WA 2002. Probing the free-energy surface for protein folding with single-molecule fluorescence spectroscopy. Nature 419:743–47
    [Google Scholar]
  122. 122.  Segel DJ, Fink AL, Hodgson KO, Doniach S 1998. Protein denaturation: a small-angle X-ray scattering study of the ensemble of unfolded states of cytochrome c. Biochemistry 37:12443–51
    [Google Scholar]
  123. 123.  Semisotnov GV, Kihara H, Kotova NV, Kimura K, Amemiya Y et al. 1996. Protein globularization during folding. A study by synchrotron small-angle X-ray scattering. J. Mol. Biol. 262:559–74
    [Google Scholar]
  124. 124.  Sen S, Goluguri RR, Udgaonkar JB 2017. A dry transition state more compact than the native state is stabilized by non-native interactions during the unfolding of a small protein. Biochemistry 56:3699–703
    [Google Scholar]
  125. 125.  Shakhnovich EI, Finkelstein AV 1989. Theory of cooperative transitions in protein molecules. I. Why denaturation of globular protein is a first-order phase transition. Biopolymers 28:1667–80
    [Google Scholar]
  126. 126.  Shin Y, Brangwynne CP 2017. Liquid phase condensation in cell physiology and disease. Science 357:eaaf4382
    [Google Scholar]
  127. 127.  Sherman E, Haran G 2006. Coil-globule transition in the denatured state of a small protein. PNAS 103:11539–43
    [Google Scholar]
  128. 128.  Shortle D, Ackerman MS 2001. Persistence of native-like topology in a denatured protein in 8 M urea. Science 293:487–89
    [Google Scholar]
  129. 129.  Song J, Gomes G-N, Shi T, Gradinaru CC, Chan HS 2017. Conformational heterogeneity and FRET data interpretation for dimensions of unfolded proteins. Biophys. J. 113:1012–24
    [Google Scholar]
  130. 130.  Sosnick TR, Barrick D 2011. The folding of single domain proteins—have we reached a consensus?. Curr. Opin. Struct. Biol. 21:12–24
    [Google Scholar]
  131. 131.  Steinhauser MO. 2005. A molecular dynamics study on universal properties of polymer chains in different solvent qualities. Part I. A review of linear chain properties. J. Chem. Phys. 122:094901
    [Google Scholar]
  132. 132.  Tanford C. 1968. Protein denaturation. Adv. Protein Chem. 23:121–282
    [Google Scholar]
  133. 133.  Teufel DP, Johnson CM, Lum JK, Neuweiler H 2011. Backbone-driven collapse in unfolded protein chains. J. Mol. Biol. 409:250–62
    [Google Scholar]
  134. 134.  Thirumalai D, Liu Z, O'Brien EP, Reddy G 2013. Protein folding: from theory to practice. Curr. Opin. Struct. Biol. 23:22–29
    [Google Scholar]
  135. 135.  Tooke L, Duitch L, Measey TJ, Schweitzer-Stenner R 2010. Kinetics of the self-aggregation and film formation of poly-L-proline at high temperatures explored by circular dichroism spectroscopy. Biopolymers 93:451–57
    [Google Scholar]
  136. 136.  Tran HT, Mao A, Pappu RV 2008. Role of backbone–solvent interactions in determining conformational equilibria of intrinsically disordered proteins. J. Am. Chem. Soc. 130:7380–92
    [Google Scholar]
  137. 137.  van der Lee R, Buljan M, Lang B, Weatheritt RJ, Daughdrill GW et al. 2014. Classification of intrinsically disordered regions and proteins. Chem. Rev. 114:6589–631
    [Google Scholar]
  138. 138.  Vitalis A, Caflisch A 2010. Micelle-like architecture of the monomer ensemble of Alzheimer's amyloid-β peptide in aqueous solution and its implications for Aβ aggregation. J. Mol. Biol. 403:148–65
    [Google Scholar]
  139. 139.  Vitalis A, Wang X, Pappu RV 2007. Quantitative characterization of intrinsic disorder in polyglutamine: insights from analysis based on polymer theories. Biophys. J. 93:1923–37
    [Google Scholar]
  140. 140.  Vitalis A, Wang X, Pappu RV 2008. Atomistic simulations of the effects of polyglutamine chain length and solvent quality on conformational equilibria and spontaneous homodimerization. J. Mol. Biol. 384:279–97
    [Google Scholar]
  141. 141.  Wallqvist A, Covell DG, Thirumalai D 1998. Hydrophobic interactions in aqueous urea solutions with implications for the mechanism of protein denaturation. J. Am. Chem. Soc. 120:427–28
    [Google Scholar]
  142. 142.  Walters BT, Mayne L, Hinshaw JR, Sosnick TR, Englander SW 2013. Folding of a large protein at high structural resolution. PNAS 110:18898–903
    [Google Scholar]
  143. 143.  Wei M-T, Elbaum-Garfinkle S, Holehouse AS, Chen CC-H, Feric M et al. 2017. Phase behaviour of disordered proteins underlying low density and high permeability of liquid organelles. Nat. Chem. 9:1118–25
    [Google Scholar]
  144. 144.  Wilkins DK, Grimshaw SB, Receveur V, Dobson CM, Jones JA, Smith LJ 1999. Hydrodynamic radii of native and denatured proteins measured by pulse field gradient NMR techniques. Biochemistry 38:16424–31
    [Google Scholar]
  145. 145.  Williamson TE, Vitalis A, Crick SL, Pappu RV 2010. Modulation of polyglutamine conformations and dimer formation by the N-terminus of huntingtin. J. Mol. Biol. 396:1295–309
    [Google Scholar]
  146. 146.  Wolfenden R. 1978. Interaction of the peptide bond with solvent water: a vapor phase analysis. Biochemistry 17:201–4
    [Google Scholar]
  147. 147.  Wright PE, Dyson HJ 1999. Intrinsically unstructured proteins: re-assessing the protein structure-function paradigm. J. Mol. Biol. 293:321–31
    [Google Scholar]
  148. 148.  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
    [Google Scholar]
  149. 149.  Yarawsky AE, English LR, Whitten ST, Herr AB 2017. The proline/glycine-rich region of the biofilm adhesion protein Aap forms an extended stalk that resists compaction. J. Mol. Biol. 429:261–79
    [Google Scholar]
  150. 150.  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
    [Google Scholar]
  151. 151.  Zhang G, Wu C 2006. Folding and formation of mesoglobules in dilute copolymer solutions. Conformation-Dependent Design of Sequences in Copolymers I AR Khokhlov 101–76 Berlin, Ger.: Springer-Verlag Berl. Heidelb.
    [Google Scholar]
  152. 152.  Zheng W, Borgia A, Buholzer K, Grishaev A, Schuler B, Best RB 2016. Probing the action of chemical denaturant on an intrinsically disordered protein by simulation and experiment. J. Am. Chem. Soc. 138:11702–13
    [Google Scholar]
  153. 153.  Ziv G, Thirumalai D, Haran G 2009. Collapse transition in proteins. Phys. Chem. Chem. Phys. 11:83–93
    [Google Scholar]
/content/journals/10.1146/annurev-biophys-070317-032838
Loading
/content/journals/10.1146/annurev-biophys-070317-032838
Loading

Data & Media loading...

  • Article Type: Review Article
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