1932
0
  1. Home
  2. A-Z Publications
  3. Annual Review of Biophysics
  4. Volume 45, 2016
  5. Article

Annual Review of Biophysics

Volume 45, 2016

Protein Folding—How and Why: By Hydrogen Exchange, Fragment Separation, and Mass Spectrometry

Abstract

Advanced hydrogen exchange (HX) methodology can now determine the structure of protein folding intermediates and their progression in folding pathways. Key developments over time include the HX pulse labeling method with nuclear magnetic resonance analysis, the fragment separation method, the addition to it of mass spectrometric (MS) analysis, and recent improvements in the HX MS technique and data analysis. Also, the discovery of protein foldons and their role supplies an essential interpretive link. Recent work using HX pulse labeling with MS analysis finds that a number of proteins fold by stepping through a reproducible sequence of native-like intermediates in an ordered pathway. The stepwise nature of the pathway is dictated by the cooperative foldon unit construction of the protein. The pathway order is determined by a sequential stabilization principle; prior native-like structure guides the formation of adjacent native-like structure. This view does not match the funneled energy landscape paradigm of a very large number of folding tracks, which was framed before foldons were known and is more appropriate for the unguided residue-level search to surmount an initial kinetic barrier rather than for the overall unfolded-state to native-state folding pathway.

Keyword(s): energy landscape theory, HX MS, hydrogen exchange, protein folding
Loading

Article metrics loading...

/content/journals/10.1146/annurev-biophys-062215-011121
2016-07-05
2024-04-16
Loading full text...

Full text loading...

/deliver/fulltext/biophys/45/1/annurev-biophys-062215-011121.html?itemId=/content/journals/10.1146/annurev-biophys-062215-011121&mimeType=html&fmt=ahah

Literature Cited

  1. Anfinsen CB, Haber E, Sela M, White FH Jr. 1.  1961. The kinetics of formation of native ribonuclease during oxidation of the reduced polypeptide chain. PNAS 47:1309–14 [Google Scholar]
  2. Bai Y, Englander SW. 2.  1996. Future directions in folding: the multi-state nature of protein structure. Proteins 24:145–51 [Google Scholar]
  3. Bai Y, Milne JS, Mayne L, Englander SW. 3.  1993. Primary structure effects on peptide group hydrogen exchange. Proteins 17:75–86 [Google Scholar]
  4. Bai Y, Milne JS, Mayne L, Englander SW. 4.  1994. Protein stability parameters measured by hydrogen exchange. Proteins 20:4–14 [Google Scholar]
  5. Bai Y, Sosnick TR, Mayne L, Englander SW. 5.  1995. Protein folding intermediates: native-state hydrogen exchange. Science 269:192–97 [Google Scholar]
  6. Baldwin RL.6.  2008. The search for folding intermediates and the mechanism of protein folding. Annu. Rev. Biophys. 37:1–21 [Google Scholar]
  7. Baldwin RL.7.  2011. Early days of protein hydrogen exchange: 1954–1972. Proteins 79:2021–26 [Google Scholar]
  8. Bieri O, Wildegger G, Bachmann A, Wagner C, Kiefhaber T. 8.  1999. A salt-induced kinetic intermediate is on a new parallel pathway of lysozyme folding. Biochemistry 38:12460–70 [Google Scholar]
  9. Bollen YJ, Kamphuis MB, van Mierlo CP. 9.  2006. The folding energy landscape of apoflavodoxin is rugged: Hydrogen exchange reveals nonproductive misfolded intermediates. PNAS 103:4095–100 [Google Scholar]
  10. Chamberlain AK, Marqusee S. 10.  2000. Comparison of equilibrium and kinetic approaches for determining protein folding mechanisms. Adv. Protein Chem. 53:283–328 [Google Scholar]
  11. Connelly GP, Bai Y, Jeng MF, Englander SW. 11.  1993. Isotope effects in peptide group hydrogen exchange. Proteins 17:87–92 [Google Scholar]
  12. Dill KA, Chan HS. 12.  1997. From Levinthal to pathways to funnels. Nat. Struct. Biol. 4:10–19 [Google Scholar]
  13. Eigen M.13.  1964. Proton transfer, acid-base catalysis, and enzymatic hydrolysis. Angew. Chem. Int. Ed. Engl. 3:1–19 [Google Scholar]
  14. Englander JJ, Rogero JR, Englander SW. 14.  1985. Protein hydrogen exchange studied by the fragment separation method. Anal. Biochem. 147:234–44 [Google Scholar]
  15. Englander SW.15.  1963. A hydrogen exchange method using tritium and Sephadex. Application to ribonuclease. Biochemistry 2:798–807 [Google Scholar]
  16. Englander SW.16.  2000. Protein folding intermediates and pathways studied by hydrogen exchange. Annu. Rev. Biophys. Biomol. Struct. 29:213–38 [Google Scholar]
  17. Englander SW.17.  2006. Hydrogen exchange and mass spectrometry: a historical perspective. J. Am. Soc. Mass Spectrom. 17:1481–89 [Google Scholar]
  18. Englander SW, Calhoun Englander DB JJ, Kallenbach NR, Liem RKH. 18.  et al. 1980. Individual breathing reactions measured in hemoglobin by hydrogen exchange methods. Biophys. J. 32:577–89 [Google Scholar]
  19. Englander SW, Englander JJ. 19.  1983. Functional labeling in hemoglobin. Structure and Dynamics: Nucleic Acids and Proteins E Clementi, RH Sarma 421–34 Guilderland, NY: Adenine [Google Scholar]
  20. Englander SW, Kallenbach NR. 20.  1983. Hydrogen exchange and structural dynamics of proteins and nucleic acids. Q. Rev. Biophys. 16:521–655 [Google Scholar]
  21. Englander SW, Mayne L. 21.  2014. The nature of protein folding pathways. PNAS 111:15873–80 [Google Scholar]
  22. Feng H, Zhou Z, Bai Y. 22.  2005. A protein folding pathway with multiple folding intermediates at atomic resolution. PNAS 102:5026–31 [Google Scholar]
  23. Fenn JB, Mann M, Meng CK, Wong SF, Whitehouse CM. 23.  1989. Electrospray ionization for mass spectrometry of large biomolecules. Science 246:64–71 [Google Scholar]
  24. Fleming PJ, Rose GD. 24.  2005. Do all backbone polar groups in proteins form hydrogen bonds?. Protein Sci. 14:1911–17 [Google Scholar]
  25. Fuentes EJ, Wand AJ. 25.  1998. Local stability and dynamics of apocytochrome b562 examined by the dependence of hydrogen exchange on hydrostatic pressure. Biochemistry 37:9877–83 [Google Scholar]
  26. Hernandez G, LeMaster DM. 26.  2009. NMR analysis of native-state protein conformational flexibility by hydrogen exchange. Methods Mol. Biol. 490:285–310 [Google Scholar]
  27. Hu W, Walters BT, Kan ZY, Mayne L, Rosen LE. 27.  et al. 2013. Stepwise protein folding at near amino acid resolution by hydrogen exchange and mass spectrometry. PNAS 110:7684–89 [Google Scholar]
  28. Huyghues-Despointes BM, Scholtz JM, Pace CN. 28.  1999. Protein conformational stabilities can be determined from hydrogen exchange rates. Nat. Struct. Biol. 6:910–12 [Google Scholar]
  29. Hvidt A, Nielsen SO. 29.  1966. Hydrogen exchange in proteins. Adv. Protein Chem. 21:287–386 [Google Scholar]
  30. Kan ZY, Mayne L, Chetty PS, Englander SW. 30.  2011. ExMS: data analysis for HX-MS experiments. J. Am. Soc. Mass Spectrom. 22:1906–15 [Google Scholar]
  31. Kan ZY, Walters BT, Mayne L, Englander SW. 31.  2013. Protein hydrogen exchange at residue resolution by proteolytic fragmentation mass spectrometry analysis. PNAS 110:16438–43 [Google Scholar]
  32. Krishna MMG, Lin Y, Rumbley JN, Englander SW. 32.  2003. Cooperative omega loops in cytochrome c: role in folding and function. J. Mol. Biol. 331:29–36 [Google Scholar]
  33. Leopold PE, Montal M, Onuchic JN. 33.  1992. Protein folding funnels: a kinetic approach to the sequence-structure relationship. PNAS 89:8721–25 [Google Scholar]
  34. Levinthal C.34.  1968. Are there pathways for protein folding?. J. Chim. Phys. 65:44–45 [Google Scholar]
  35. Levinthal C.35.  1969. How to fold graciously Presented at Mossbauer Spectrosc. in Biol. Syst. Monticello, IL: University of Illinois Bulletin
  36. Linderstrøm-Lang K.36.  1958. Deuterium exchange and protein structure. Symposium on Protein Structure A Neuberger 23–34 London: Methuen
  37. Linderstrøm-Lang KU, Schellman JA. 37.  1959. Protein structure and enzyme activity. The Enzymes PD Boyer, H Lardy, K Myrback 443–510 New York: Academic [Google Scholar]
  38. Maity H, Lim WK, Rumbley JN, Englander SW. 38.  2003. Protein hydrogen exchange mechanism: local fluctuations. Protein Sci. 12:153–60 [Google Scholar]
  39. Maity H, Maity M, Englander SW. 39.  2004. How cytochrome c folds, and why: submolecular foldon units and their stepwise sequential stabilization. J. Mol. Biol. 343:223–33 [Google Scholar]
  40. Maity H, Maity M, Krishna MM, Mayne L, Englander SW. 40.  2005. Protein folding: the stepwise assembly of foldon units. PNAS 102:4741–46 [Google Scholar]
  41. Maity M, Maity H, Englander SW. 41.  2004. A stepwise sequential folding/unfolding pathway in cytochrome c. Biophys. J. 86:Suppl.498A [Google Scholar]
  42. Mayne L, Kan ZY, Chetty PS, Ricciuti A, Walters BT, Englander SW. 42.  2011. Many overlapping peptides for protein hydrogen exchange experiments by the fragment separation-mass spectrometry method. J. Am. Soc. Mass Spectrom. 22:1898–905 [Google Scholar]
  43. Milne JS, Mayne L, Roder H, Wand AJ, Englander SW. 43.  1998. Determinants of protein hydrogen exchange studied in equine cytochrome c. Protein Sci. 7:739–45 [Google Scholar]
  44. Molday RS, Englander SW, Kallen RG. 44.  1972. Primary structure effects on peptide group hydrogen exchange. Biochemistry 11:150–58 [Google Scholar]
  45. Molday RS, Kallen RG. 45.  1972. Substituent effects on amide hydrogen exchange rates in aqueous solution. J. Am. Chem. Soc. 94:6739–45 [Google Scholar]
  46. Nickson AA, Wensley BG, Clarke J. 46.  2013. Take home lessons from studies of related proteins. Curr. Opin. Struct. Biol. 23:66–74 [Google Scholar]
  47. Panchenko AR, Luthey-Schulten Z, Wolynes PG. 47.  1996. Foldons, protein structural modules, and exons. PNAS 93:2008–13 [Google Scholar]
  48. Perrin CL, Lollo CP. 48.  1984. Mechanisms of NH proton exchange in amide and proteins: solvent effects and solvent accessibility. J. Am. Chem. Soc. 106:2754–57 [Google Scholar]
  49. Pirrone GF, Iacob RE, Engen JR. 49.  2015. Applications of hydrogen/deuterium exchange MS from 2012 to 2014. Anal. Chem. 87:99–118 [Google Scholar]
  50. Roder H, Elöve GA, Englander SW. 50.  1988. Structural characterization of folding intermediates in cytochrome c by H-exchange labelling and proton NMR. Nature 335:700–4 [Google Scholar]
  51. Rogero JR, Englander JJ, Englander SW. 51.  1986. Individual breathing reactions measured by functional labeling and hydrogen exchange methods. Methods Enzymol. 131:508–17 [Google Scholar]
  52. Rosa JJ, Richards FM. 52.  1979. An experimental procedure for increasing the structural resolution of chemical hydrogen exchange measurements on proteins: application to ribonuclease S peptide. J. Mol. Biol. 133:399–416 [Google Scholar]
  53. Rosenberg A, Chakravarti K. 53.  1968. Studies of hydrogen exchange in proteins. I. The exchange kinetics of bovine carbonic anhydrase. J. Biol. Chem. 243:5193–201 [Google Scholar]
  54. Rosenberg A, Enberg J. 54.  1969. Studies of hydrogen exchange in proteins. II. The reversible thermal unfolding of chymotrypsinogen A as studied by exchange kinetics. J. Biol. Chem. 244:6153–59 [Google Scholar]
  55. Silverman JA, Harbury PB. 55.  2002. The equilibrium unfolding pathway of a (β/α)8 barrel. J. Mol. Biol. 324:1031–40 [Google Scholar]
  56. Skinner JJ, Lim WK, Bedard S, Black BE, Englander SW. 56.  2012. Protein dynamics viewed by hydrogen exchange. Protein Sci. 21:996–1005 [Google Scholar]
  57. Skinner JJ, Lim WK, Bedard S, Black BE, Englander SW. 57.  2012. Protein hydrogen exchange: testing current models. Protein Sci. 21:987–95 [Google Scholar]
  58. Sosnick TR, Barrick D. 58.  2011. The folding of single domain proteins—have we reached a consensus?. Curr. Opin. Struct. Biol. 21:12–24 [Google Scholar]
  59. Udgaonkar JB, Baldwin RL. 59.  1990. Early folding intermediate of ribonuclease A. PNAS 87:8197–201 [Google Scholar]
  60. Udgaonkar JB, Baldwin RL. 60.  1995. Nature of the early folding intermediate of ribonuclease A. Biochemistry 34:4088–96 [Google Scholar]
  61. Wagner G, Wüthrich K. 61.  1982. Amide proton exchange and surface conformation of BPTI in solution: studies with 2D NMR. J. Mol. Biol. 160:343–61 [Google Scholar]
  62. Walters BT, Mayne L, Hinshaw JR, Sosnick TR, Englander SW. 62.  2013. Folding of a large protein at high structural resolution. PNAS 110:18898–903 [Google Scholar]
  63. Walters BT, Ricciuti A, Mayne L, Englander SW. 63.  2012. Minimizing back exchange in the hydrogen exchange-mass spectrometry experiment. J. Am. Soc. Mass Spectrom. 23:2132–39 [Google Scholar]
  64. Wand AJ, Roder H, Altman S, Englander SW. 64.  1985. Amide proton exchange in reduced and oxidized cytochrome c by 2-dimensional NMR Presented at Annu. Meet. Biophys. Soc., 29th, Feb. 24–28, Baltimore, MD
  65. Weinkam P, Zong C, Wolynes PG. 65.  2005. A funneled energy landscape for cytochrome c directly predicts the sequential folding route inferred from hydrogen exchange experiments. PNAS 102:12401–6 [Google Scholar]
  66. Wolynes PG, Onuchic JN, Thirumalai D. 66.  1995. Navigating the folding routes. Science 267:1619–20 [Google Scholar]
  67. Woodward CK, Hilton BD, Tuchsen E. 67.  1982. Hydrogen exchange and the dynamic structure of proteins. Mol. Cell. Biochem. 48:135–60 [Google Scholar]
  68. Yan S, Kennedy SD, Koide S. 68.  2002. Thermodynamic and kinetic exploration of the energy landscape of Borrelia burgdorferi OspA by native-state hydrogen exchange. J. Mol. Biol. 323:363–75 [Google Scholar]
  69. Zhang Z, Smith DL. 69.  1993. Determination of amide hydrogen exchange by mass spectrometry: a new tool for protein structure elucidation. Protein Sci. 2:522–31 [Google Scholar]
/content/journals/10.1146/annurev-biophys-062215-011121
Loading
Protein Folding—How and Why: By Hydrogen Exchange, Fragment Separation, and Mass Spectrometry
Annual Review of Biophysics 45, 135 (2016); https://doi.org/10.1146/annurev-biophys-062215-011121
/content/journals/10.1146/annurev-biophys-062215-011121
/content/journals/10.1146/annurev-biophys-062215-011121
Loading

Data & Media loading...

  • Article Type: Review Article

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