Journal of Molecular Evolution

, Volume 73, Issue 3–4, pp 166–180 | Cite as

Amphiphilic α-Helical Potential: A Putative Folding Motif Adding Few Constraints to Protein Evolution

Article

Abstract

Evidence from a number of studies indicates that protein folding is dictated not only by factors stabilizing the native state, but also by potentially independent factors that create folding pathways. How natural selection might cope simultaneously with two independent factors was addressed in this study within the framework of the “Lim-model” of protein folding, which postulates that the early stages of folding of all globular proteins, regardless of their native structure, are directed at least in part by potential to form amphiphilic α-helices. For this purpose, the amphiphilic α-helical potential in randomly ordered amino acid sequences and the conservation in phylogeny of amphiphilic α-helical potential within various proteins were assessed. These analyses revealed that amphiphilic α-helical potential is a common occurrence in random sequences, and that the presence of amphiphilic α-helical potential is present but not conserved in phylogeny within a given protein. The results suggest that the rapid formation of molten globules and the variable behavior of those globules depending on the protein may be a fundamental property of polymers of naturally occurring amino acids more so than a trait that must be derived or maintained by natural selection. Further, the results point toward the utility of randomly occurring process in protein function and evolution, and suggest that the formation of efficient pathways that determine early processes in protein folding, unlike the formation of stable, native protein structure, does not present a substantial hurdle during the evolution of amino acid sequences.

Keywords

Protein folding Helical intermediate Evolution Amphiphilic Randomly occurring processes Trifluoroethanol (TFE) 

References

  1. Bridgham JT, Ortlund EA, Thornton JW (2009) An epistatic ratchet constrains the direction of glucocorticoid receptor evolution. Nature 461:515PubMedCrossRefGoogle Scholar
  2. Brown NP, Leroy C, Sander C (1998) MView: a web-compatible database search or multiple alignment viewer. Bioinformatics 14:380PubMedCrossRefGoogle Scholar
  3. Burns LL, Dalessio PM, Ropson IJ (1998) Folding mechanism of three structurally similar beta-sheet proteins. Proteins 33:107PubMedCrossRefGoogle Scholar
  4. Chen E, Everett ML, Holzknecht ZE, Holzknecht RA, Lin SS, Bowles DE, Parker W (2010) Short-lived alpha-helical intermediates in the folding of beta-sheet proteins. Biochemistry 49:5609–5619PubMedCrossRefGoogle Scholar
  5. Chenna R, Sugawara H, Koike T, Lopez R, Gibson TJ, Higgins DG, Thompson JD (2003) Multiple sequence alignment with the Clustal series of programs. Nucleic Acids Res 31:3497PubMedCrossRefGoogle Scholar
  6. Eisenberg D (1984) Three-dimensional structure of membrane and surface proteins. Annu Rev Biochem 53:595PubMedCrossRefGoogle Scholar
  7. Eisenberg D, Schwarz E, Komaromy M, Wall R (1984) Analysis of membrane and surface protein sequences with the hydrophobic moment plot. J Mol Biol 179:125PubMedCrossRefGoogle Scholar
  8. Gonnet GH, Cohen MA, Benner SA (1992) Exhaustive matching of the entire protein sequence database. Science (Washington D C) 256:1443CrossRefGoogle Scholar
  9. Hamada D, Goto Y (1997) The equilibrium intermediate of beta-lactoglobulin with non-native alpha-helical structure. J Mol Biol 269:479PubMedCrossRefGoogle Scholar
  10. Hamada D, Segawa S-I, Goto Y (1996) Non-native alpha-helical intermediate in the refolding of beta-lactoglobulin, a predominantly beta-sheet protein. Nat Struct Biol 3:868PubMedCrossRefGoogle Scholar
  11. Hamada D, Chiti F, Guijarro JI, Kataoka M, Taddei N, Dobson CM (2000) Evidence concerning rate-limiting steps in protein folding from the effects of trifluoroethanol. Nat Struct Biol 7:58PubMedCrossRefGoogle Scholar
  12. Larios E, Li JS, Schulten K, Kihara H, Gruebele M (2004) Multiple probes reveal a native-like intermediate during low-temperature refolding of ubiquitin. J Mol Biol 340:115PubMedCrossRefGoogle Scholar
  13. Lattman EE, Rose GD (1993) Protein folding—what’s the question? Proc Natl Acad Sci USA 90:439PubMedCrossRefGoogle Scholar
  14. Li J, Shinjo M, Matsumura Y, Morita M, Baker D, Ikeguchi M, Kihara H (2007) An alpha-helical burst in the src SH3 folding pathway. Biochemistry 46:5072PubMedCrossRefGoogle Scholar
  15. Lim VI (1978a) Polypeptide chain folding through a highly helical intermediate as a general principle of globular protein structure formation. FEBS Lett 89:10PubMedCrossRefGoogle Scholar
  16. Lim VI (1978b) Stereochemical theory of the 3 dimensional structure of globular proteins. Part 2 Transition of the highly helical intermediate structure into the native one. Mol Biol (Moscow) 12:214Google Scholar
  17. Lim VI, Mazanov AL, Efimov AV (1978) Stereochemical theory of the 3 dimensional structure of globular proteins. Part 1 Highly helical intermediate structures. Mol Biol (Moscow) 12:206Google Scholar
  18. Liu J, Song J (2008) NMR evidence for forming highly populated helical conformations in the partially folded hNck2 SH3 domain. Biophys J 95:4803PubMedCrossRefGoogle Scholar
  19. Parker W, Song PS (1990) Location of helical regions in tetrapyrrole-containing proteins by a helical hydrophobic moment analysis. Application to phytochrome. J Biol Chem 265:17568PubMedGoogle Scholar
  20. Parker W, Stezowski JJ (1996) The surface of beta-sheet proteins contains amphiphilic regions which may provide clues about protein folding. Proteins 25:253PubMedGoogle Scholar
  21. Parker W, Sood A, Song A (2001) Organization of regions with amphiphilic alpha-helical potential within the three-dimensional structure of beta-sheet proteins. Protein Eng 14:315PubMedCrossRefGoogle Scholar
  22. Pironio S, Acin A, Massar S, de la Giroday AB, Matsukevich DN, Maunz P, Olmschenk S, Hayes D, Luo L, Manning TA, Monroe C (2010) Random numbers certified by Bell’s theorem. Nature 464:1021PubMedCrossRefGoogle Scholar
  23. Ropson IJ, Gordon JI, Frieden C (1990) Folding of a predominantly beta-structure protein: rat intestinal fatty acid binding protein. Biochemistry 29:9591PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2011

Authors and Affiliations

  1. 1.Department of SurgeryDuke University Medical CenterDurhamUSA

Personalised recommendations