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Chinese Journal of Polymer Science

, Volume 37, Issue 7, pp 708–718 | Cite as

Evolution of Conformation and Dynamics of Solvents in Hydration Shell along the Urea-induced Unfolding of Ubiquitin

  • Ke-Cheng Yang
  • Feng-Chao CuiEmail author
  • Ce Shi
  • Wen-Duo Chen
  • Yun-Qi LiEmail author
Article
  • 25 Downloads

Abstract

A clear diagram for the unfolding of protein induced by denaturant is a classical but still unsolved challenge. To explore the unfolded conformations of ubiquitin under different urea concentrations, we performed hybrid Monte Carlo-molecular dynamics simulations (MC-MD) guided by small angle X-ray scattering (SAXS) structural information. Conformational ensembles sampled by the hybrid MC-MD algorithm exhibited typical 3D structures at different urea concentrations. These typical structures suggested that ubiquitin was subjected to a sequential unfolding, where the native contacts between adjacent β-sheets at first were disrupted together with the exposure of hydrophobic core, followed by the conversion of remaining β-strands and helices into random coils. Ubiquitin in 8 mol·L−1 urea is almost a random coil. With the disruption of native structure, urea molecules are enriched at protein hydrated layer to stabilize newly exposed residues. Compared with water, urea molecules prefer to form hydrogen bonds with the backbone of ubiquitin, thus occupying nodes of the hydrogen bonding network that construct the secondary structure of proteins. Meanwhile, we also found that the slow dynamics of urea molecules was almost unchanged while the dynamics of water was accelerated in the hydration shell when more residues were unfolded and exposed. The former was also responsible for the stabilization of unfolded structures.

Keywords

Ubiquitin Unfolding process Hydration behavior and dynamics Water and urea 

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Notes

Acknowledgments

This work was financially supported by the National Natural Science Foundation of China (Nos. 21504092 and U1832177), and One Hundred Person Project of the Chinese Academy of Sciences. We are also grateful to Computing Center of Jilin Province and Henan Province Supercomputer Center for essential support.

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10118_2019_2238_MOESM1_ESM.pdf (992 kb)
Evolution of Conformation and Dynamics of Solvents in Hydration Shell along the Urea-induced Unfolding of Ubiquitin

References

  1. 1.
    Schlesinger, D. H.; Goldstein, G. Molecular conservation of 74 amino acid sequence of ubiquitin between cattle and man. Nature 1975, 2, 423–424CrossRefGoogle Scholar
  2. 2.
    Goldstein, G.; Scheid, M.; Hammerling, U.; Schlesinger, D. H.; Niall, H. D.; Boyse, E. A. Isolation of a polypeptide that has lymphocyte-differentiating properties and is probably represented universally in living cells. Proc. Natl. Acad. Sci. 1975, 72, 11–5CrossRefGoogle Scholar
  3. 3.
    Hershko, A.; Eytan, E.; Ciechanover, A.; Haas, A. L. Immunochemical analysis of the turnover of ubiquitin-protein conjugates in intact cells. Relationship to the breakdown of abnormal proteins. J. Biol. Chem. 1982, 257, 13964–70Google Scholar
  4. 4.
    Vijay-Kumar, S.; Bugg, C. E.; Cook, W. J. Structure of ubiquitin refined at 1.8 Å resolution. J. Mol. Biol. 1987, 194, 531–544CrossRefGoogle Scholar
  5. 5.
    Sillitoe, I.; Lewis, T. E.; Cuff, A.; Das, S.; Ashford, P.; Dawson, N. L.; Furnham, N.; Laskowski, R. A.; Lee, D.; Lees, J. G.; Lehtinen, S.; Studer, R. A.; Thornton, J.; Orengo, C. A. CATH: Comprehensive structural and functional annotations for genome sequences. Nucleic Acids Res. 2015, 43, D376–D381.CrossRefGoogle Scholar
  6. 6.
    Reddy, G.; Thirumalai, D. Collapse precedes folding in denaturant-dependent assembly of ubiquitin. J. Phys. Chem. B 2017, 121, 995–1009CrossRefGoogle Scholar
  7. 7.
    Piana, S.; Lindorff-Larsen, K.; Shaw, D. E. Atomic-level description of ubiquitin folding. Proc. Natl. Acad. Sci. 2013, 110, 5915–5920CrossRefGoogle Scholar
  8. 8.
    Makhatadze, G. I.; Lopez, M. M.; Richardson, J. M.; Thmos, S. T. Anion binding to the ubiquitin molecule. Protein Sci. 1998, 7, 689–697CrossRefGoogle Scholar
  9. 9.
    Jacob, J.; Krantz, B.; Dothager, R. S.; Thiyagarajan, P.; Sosnick, T. R. Early collapse is not an obligate step in protein folding. J. Mol. Biol. 2004, 2, 369–82CrossRefGoogle Scholar
  10. 10.
    Wirmer, J.; Peti, W.; Schwalbe, H. M otional properties of unfolded ubiquitin: A model for a random coil protein. J. Biomol. NMR 2006, 2, 175–186CrossRefGoogle Scholar
  11. 11.
    Walters, J.; Milam, S. L.; Clark, A. C. Practical approaches to protein folding and assembly: Spectroscopic strategies in thermodynamics and kinetics. In Methods Enzymol., ed. by Michael L. Johnson, J. M. H., Gary K. Ackers, Academic Press, 2009, Vol. 455, pp 1–39.CrossRefGoogle Scholar
  12. 12.
    Vallée-Bélisle, A.; Michnick, S. W. Visualizing transient protein- folding intermediates by tryptophan-scanning mutagenesis. Nat. Struct. Mol. Biol. 2012, 19, 731–736CrossRefGoogle Scholar
  13. 13.
    Aznauryan, M.; Delgado, L.; Soranno, A.; Nettels, D.; Huang, J. R.; Labhardt, A. M.; Grzesiek, S.; Schuler, B. Comprehensive structural and dynamical view of an unfolded protein from the combination of single-molecule FRET, NMR, and SAXS. Proc. Natl. Acad. Sci. 2016, 113, E5389–E5398.CrossRefGoogle Scholar
  14. 14.
    Esteban-Martín, S.; Fenwick, R. B.; Salvatella, X. Refinement of ensembles describing unstructured proteins using NMR residual dipolar couplings. J. Am. Chem. Soc. 2010, 132, 4626–4632CrossRefGoogle Scholar
  15. 15.
    Mandal, M.; Mukhopadhyay, C. Microsecond molecular dynamics simulation of guanidinium chloride induced unfolding of ubiquitin. Phys. Chem. Chem. Phys. 2014, 16, 21706–21716CrossRefGoogle Scholar
  16. 16.
    Hua, L.; Zhou, R.; Thirumalai, D.; Berne, B. J. Urea denaturation by stronger dispersion interactions with proteins than water implies a 2-stage unfolding. Proc. Natl. Acad. Sci. 2008, 105, 16928–16933CrossRefGoogle Scholar
  17. 17.
    Stirnemann, G.; Kang, S. G.; Zhou, R.; Berne, B. J. How force unfolding differs from chemical denaturation. Proc. Natl. Acad. Sci. 2014, 111, 3413–3418CrossRefGoogle Scholar
  18. 18.
    Shaw, K. L.; Scholtz, J. M.; Pace, C. N.; Grimsley, R. G. in Protein structure, stability, and interactions. Vol. 490, ed. by Shriver, J. W. Humana Press, Totowa, NJ, 2009, p. 41–55.Google Scholar
  19. 19.
    Tanford, C. Isothermal unfolding of globular proteins in aqueous urea solutions. J. Am. Chem. Soc. 1964, 86, 2050–2059CrossRefGoogle Scholar
  20. 20.
    Canchi, D. R.; García, A. E. Cosolvent effects on protein stability. Annu. Rev. Phys. Chem. 2013, 2, 273–293CrossRefGoogle Scholar
  21. 21.
    Guinn, E. J.; Pegram, L. M.; Capp, M. W.; Pollock, M. N.; Record, M. T. Quantifying why urea is a protein denaturant, whereas glycine betaine is a protein stabilizer. Proc. Natl. Acad. Sci. 2011, 2, 16932–16937CrossRefGoogle Scholar
  22. 22.
    Frank, H. S.; Franks, F. Structural approach to the solvent power of water for hydrocarbons: Urea as a structure breaker. J. Chem. Phys. 1968, 48, 4746–4757CrossRefGoogle Scholar
  23. 23.
    Nayar, D.; Folberth, A.; van der Vegt, N. F. A. Molecular origin of urea driven hydrophobic polymer collapse and unfolding depending on side chain chemistry. Phys. Chem. Chem. Phys. 2017, 2, 18156–18161CrossRefGoogle Scholar
  24. 24.
    O'Brien, E. P.; Dima, R. I.; Brooks, B.; Thirumalai, D. Interactions between hydrophobic and ionic solutes in aqueous guanidinium chloride and urea solutions: Lessons for protein denaturation mechanism. J. Am. Chem. Soc. 2007, 2, 7346–7353CrossRefGoogle Scholar
  25. 25.
    Stumpe, M. C.; Grubmüller, H. Polar or apolar—The role of polarity for urea-induced protein denaturation. PLoS Comp. Biol. 2008, 4, e1000221.Google Scholar
  26. 26.
    Candotti, M.; Pérez, A.; Ferrer-Costa, C.; Rueda, M.; Meyer, T.; Gelpí, J. L.; Orozco, M. Exploring early stages of the chemical unfolding of proteins at the proteome scale. PLoS Comp. Biol. 2013, 9, e1003393.CrossRefGoogle Scholar
  27. 27.
    Stumpe, M. C.; Grubmüller, H. Urea impedes the hydrophobic collapse of partially unfolded proteins. Biophys. J. 2009, 96, 3744–3752CrossRefGoogle Scholar
  28. 28.
    Canchi, D. R.; García, Angel E. Backbone and side-chain contributions in protein denaturation by urea. Biophys. J. 2011, 100, 1526–1533CrossRefGoogle Scholar
  29. 29.
    Smolin, N.; Voloshin, V. P.; Anikeenko, A. V.; Geiger, A.; Winter, R.; Medvedev, N. N. TMAO and urea in the hydration shell of the protein SNase. Phys. Chem. Chem. Phys. 2017, 19, 6345–6357.CrossRefGoogle Scholar
  30. 30.
    Yang, K.; Cui, F.; Li, Y. Distribution and dynamics of water and urea in hydration shell of ribonuclease Sa: A molecular dynamics simulation study. Chinese Journal of Applied Chemistry 2018, 35, 1243–1248Google Scholar
  31. 31.
    Biedermannová, L.; Schneider, B. Hydration of proteins and nucleic acids: Advances in experiment and theory. A review. Biochim. Biophys. Acta 2016, 2, 1821–1835CrossRefGoogle Scholar
  32. 32.
    Gavrilov, Y.; Leuchter, J. D.; Levy, Y. On the coupling between the dynamics of protein and water. Phys. Chem. Chem. Phys. 2017, 19, 8243–8257CrossRefGoogle Scholar
  33. 33.
    Del Galdo S.; Amadei, A. The unfolding effects on the protein hydration shell and partial molar volume: A computational study. Phys. Chem. Chem. Phys. 2016, 18, 28175–28182Google Scholar
  34. 34.
    Moron, M. C. Water dynamics on the surface of the protein barstar. Phys. Chem. Chem. Phys. 2012, 2, 15393–15399Google Scholar
  35. 35.
    Yang, K.; Rózycki, B.; Cui, F.; Shi, C.; Chen, W.; Li, Y. Sampling enrichment toward target structures using hybrid molecular dynamics-Monte Carlo simulations. PLoS One 2016, 11, e0156043.CrossRefGoogle Scholar
  36. 36.
    Hu, J.; Ma, A.; Dinner, A. R. Monte Carlo simulations of biomolecules: The MC module in CHARMM. J. Comput. Chem. 2006, 27, 203–216CrossRefGoogle Scholar
  37. 37.
    Vitalis, A.; Pappu, R. V. Methods for Monte Carlo simulations of biomacromolecules. In Annual reports in computational chemistry, Ralph, A. W., Ed. Elsevier, 2009, Vol. 5, pp 49–76.CrossRefGoogle Scholar
  38. 38.
    MacKerell, A. D.; Bashford, D.; Bellott, M.; Dunbrack, R. L.; Evanseck, J. D.; Field, M. J.; Fischer, S.; Gao, J.; Guo, H.; Ha, S.; Joseph-McCarthy, D.; Kuchnir, L.; Kuczera, K.; Lau, F. T. K.; Mattos, C.; Michnick, S.; Ngo, T.; Nguyen, D. T.; Prodhom, B.; Reiher, W. E.; Roux, B.; Schlenkrich, M.; Smith, J. C.; Stote, R.; Straub, J.; Watanabe, M.; Wiorkiewicz-Kuczera, J.; Yin, D.; Karplus, M. All-atom empirical potential for molecular modeling and dynamics studies of proteins. J. Phys. Chem. B 1998, 102, 3586–3616CrossRefGoogle Scholar
  39. 39.
    Mackerell, A. D.; Feig, M.; Brooks, C. L. Extending the treatment of backbone energetics in protein force fields: Limitations of gas-phase quantum mechanics in reproducing protein conformational distributions in molecular dynamics simulations. J. Comput. Chem. 2004, 25, 1400–1415CrossRefGoogle Scholar
  40. 40.
    Li, Y. Q.; Zhang, Y. REMO: A new protocol to refine full atomic protein models from C-alpha traces by optimizing hydrogen- bonding networks. Proteins: Struct. Funct. Bioinform. 2009, 76, 665–674CrossRefGoogle Scholar
  41. 41.
    Frishman, D.; Argos, P. Knowledge-based protein secondary structure assignment. Proteins: Struct. Funct. Bioinform. 1995, 23, 566–79CrossRefGoogle Scholar
  42. 42.
    Im, W.; Lee, M. S.; Brooks, C. L. Generalized born model with a simple smoothing function. J. Comput. Chem. 2003, 2, 1691–1702CrossRefGoogle Scholar
  43. 43.
    Weiser, J.; Shenkin, P. S.; Still, W. C. Approximate atomic surfaces from linear combinations of pairwise overlaps (LCPO). J. Comput. Chem. 1999, 2, 217–230CrossRefGoogle Scholar
  44. 44.
    Tsodikov, O. V.; Record, M. T.; Sergeev, Y. V. Novel computer program for fast exact calculation of accessible and molecular surface areas and average surface curvature. J. Comput. Chem. 2002, 2, 600–609CrossRefGoogle Scholar
  45. 45.
    Schneidman-Duhovny, D.; Hammel, M.; Sali, A. FoXS: A web server for rapid computation and fitting of SAXS profiles. Nucleic Acids Res. 2010, 38, W540–W544.CrossRefGoogle Scholar
  46. 46.
    Valentini, E.; Kikhney, A. G.; Previtali, G.; Jeffries, C. M.; Svergun, D. I. SASBDB, a repository for biological small-angle scattering data. Nucleic Acids Res. 2015, 43, D357–63.CrossRefGoogle Scholar
  47. 47.
    Huang, J. R.; Gabel, F.; Jensen, M. R.; Grzesiek, S.; Blackledge, M. Sequence-specific mapping of the interaction between urea and unfolded ubiquitin from ensemble analysis of NMR and small angle scattering data. J. Am. Chem. Soc. 2012, 134, 4429–4436CrossRefGoogle Scholar
  48. 48.
    Ribeiro, A. A.; de Alencastro, R. B. Mixed Monte Carlo/molecular dynamics simulations of the prion protein. J. Mol. Graph. Model. 2013, 42, 1–6CrossRefGoogle Scholar
  49. 49.
    Zhu, C.; Byrd, R. H.; Lu, P.; Nocedal, J. Algorithm 778: LBFGS- B: Fortran subroutines for large-scale bound-constrained optimization. ACM Trans. Math. Softw. 1997, 23, 550–560CrossRefGoogle Scholar
  50. 50.
    Morales, J. L.; Nocedal, J. Remark on "algorithm 778: LBFGS- B: Fortran subroutines for large-scale bound constrained optimization". ACM Trans. Math. Softw. 2011, 38, 1–4CrossRefGoogle Scholar
  51. 51.
    Metropolis, N.; Rosenbluth, A. W.; Rosenbluth, M. N.; Teller, A. H.; Teller, E. Equation of state calculations by fast computing machines. J. Chem. Phys. 1953, 21, 1087–1092CrossRefGoogle Scholar
  52. 52.
    Seeber, M.; Felline, A.; Raimondi, F.; Muff, S.; Friedman, R.; Rao, F.; Caflisch, A.; Fanelli, F. Wordom: A user-friendly program for the analysis of molecular structures, trajectories, and free energy surfaces. J. Comput. Chem. 2011, 32, 1183–1194CrossRefGoogle Scholar
  53. 53.
    Heyer, L. J.; Kruglyak, S.; Yooseph, S. Exploring expression data: Identification and analysis of coexpressed genes. Genome Res. 1999, 9, 1106–1115CrossRefGoogle Scholar
  54. 54.
    Phillips, J. C.; Braun, R.; Wang, W.; Gumbart, J.; Tajkhorshid, E.; Villa, E.; Chipot, C.; Skeel, R. D.; Kale, L.; Schulten, K. Scalable molecular dynamics with NAMD. J. Comput. Chem. 2005, 26, 1781–802CrossRefGoogle Scholar
  55. 55.
    Jorgensen, W. L.; Chandrasekhar, J.; Madura, J. D.; Impey, R. W.; Klein, M. L. Comparison of simple potential functions for simulating liquid water. J. Chem. Phys. 1983, 76, 926–935CrossRefGoogle Scholar
  56. 56.
    Vanommeslaeghe, K.; Hatcher, E.; Acharya, C.; Kundu, S.; Zhong, S.; Shim, J.; Darian, E.; Guvench, O.; Lopes, P.; Vorobyov, I.; Mackerell, A. D. Jr. CHARMM general force field: A force field for drug-like molecules compatible with the CHARMM all-atom additive biological force fields. J. Comput. Chem. 2010, 31, 671–90Google Scholar
  57. 57.
    Humphrey, W.; Dalke, A.; Schulten, K. VMD: Visual molecular dynamics. J. Mol. Graph. 1996, 14, 33–38CrossRefGoogle Scholar
  58. 58.
    Feller, S. E.; Zhang, Y.; Pastor, R. W.; Brooks, B. R. Constant pressure molecular dynamics simulation: The Langevin piston 58 method. J. Chem. Phys. 1995, 103, 4613–4621CrossRefGoogle Scholar
  59. 59.
    Ryckaert, J. P.; Ciccotti, G.; Berendsen, H. J. C. Numerical integration of the cartesian equations of motion of a system with constraints: Molecular dynamics of n-alkanes. J. Comput. Phys. 1977, 2, 327–341CrossRefGoogle Scholar
  60. 60.
    Candotti, M.; Esteban-Martín, S.; Salvatella, X.; Orozco, M. Toward an atomistic description of the urea-denatured state of proteins. Proc. Natl. Acad. Sci. 2013, 110, 5933–5938CrossRefGoogle Scholar
  61. 61.
    Kohn, J. E.; Millett, I. S.; Jacob, J.; Zagrovic, B.; Dillon, T. M.; Cingel, N.; Dothager, R. S.; Seifert, S.; Thiyagarajan, P.; Sosnick, T. R.; Hasan, M. Z.; Pande, V. S.; Ruczinski, I.; Doniach, S.; Plaxco, K. W. Random-coil behavior and the dimensions of chemically unfolded proteins. Proc. Natl. Acad. Sci. 2004, 101, 12491–12496CrossRefGoogle Scholar
  62. 62.
    Adzhubei, A. A.; Sternberg, M. J. E.; Makarov, A. A. Polyproline- II Helix in Proteins: Structure and Function. J. Mol. Biol. 2013, 425, 2100–2132CrossRefGoogle Scholar
  63. 63.
    Chung, H. S.; Ganim, Z.; Jones, K. C.; Tokmakoff, A. Transient 2D IR spectroscopy of ubiquitin unfolding dynamics. Proc. Natl. Acad. Sci. 2007, 104, 14237–14242CrossRefGoogle Scholar
  64. 64.
    Chung, H. S.; Shandiz, A.; Sosnick, T. R.; Tokmakoff, A. Probing the folding transition state of ubiquitin mutants by temperature- jump-induced downhill unfolding. Biochemistry 2008, 47, 13870–13877CrossRefGoogle Scholar
  65. 65.
    Lindorff-Larsen, K.; Piana, S.; Dror, R. O.; Shaw, D. E. How fast-folding proteins fold. Science 2011, 334, 517–520CrossRefGoogle Scholar
  66. 66.
    Baxa, M. C.; Freed, K. F.; Sosnick, T. R. Quantifying the structural requirements of the folding transition state of Protein A and other systems. J. Mol. Biol. 2008, 381, 1362–1381CrossRefGoogle Scholar
  67. 67.
    Sosnick, T. R.; Barrick, D. The folding of single domain proteins— Have we reached a consensus? Curr. Opin. Struct. Biol. 2011, 21, 12–24CrossRefGoogle Scholar
  68. 68.
    Daggett, V. Protein folding-simulation. Chem. Rev. 2006, 106, 1898–1916CrossRefGoogle Scholar
  69. 69.
    Qvist, J.; Ortega, G.; Tadeo, X.; Millet, O.; Halle, B. Hydration dynamics of a halophilic protein in folded and unfolded states. J. Phys. Chem. B 2012, 116, 3436–44CrossRefGoogle Scholar

Copyright information

© Chinese Chemical Society Institute of Chemistry, Chinese Academy of Sciences Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Key Laboratory of Synthetic Rubber, Changchun Institute of Applied ChemistryChinese Academy of SciencesChangchunChina
  2. 2.Smart City Research InstituteZhengzhou UniversityZhengzhouChina

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