Abstract
Progressive structuring and ultimately exclusion of water by hydrophobes surrounding backbone hydrogen bonds turn the latter into guiding factors of protein folding. Here we demonstrate that an arrangement of five hydrophobes yields an optimal hydrogen-bond stabilization. This motif is shown to be nearly ubiquitous in native folds.
Full Text
The Full Text of this article is available as a PDF (407.7 KB).
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Bahar I., Jernigan R. L. Inter-residue potentials in globular proteins and the dominance of highly specific hydrophilic interactions at close separation. J Mol Biol. 1997 Feb 14;266(1):195–214. doi: 10.1006/jmbi.1996.0758. [DOI] [PubMed] [Google Scholar]
- Baldwin Robert L. Making a network of hydrophobic clusters. Science. 2002 Mar 1;295(5560):1657–1658. doi: 10.1126/science.1069893. [DOI] [PubMed] [Google Scholar]
- Bleasby A. J., Akrigg D., Attwood T. K. OWL--a non-redundant composite protein sequence database. Nucleic Acids Res. 1994 Sep;22(17):3574–3577. [PMC free article] [PubMed] [Google Scholar]
- Bryant R. G. The dynamics of water-protein interactions. Annu Rev Biophys Biomol Struct. 1996;25:29–53. doi: 10.1146/annurev.bb.25.060196.000333. [DOI] [PubMed] [Google Scholar]
- Fernández Ariel. Time-resolved backbone desolvation and mutational hot spots in folding proteins. Proteins. 2002 Jun 1;47(4):447–457. doi: 10.1002/prot.10109. [DOI] [PubMed] [Google Scholar]
- García Angel E., Sanbonmatsu Kevin Y. Alpha-helical stabilization by side chain shielding of backbone hydrogen bonds. Proc Natl Acad Sci U S A. 2002 Feb 26;99(5):2782–2787. doi: 10.1073/pnas.042496899. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Krantz B. A., Moran L. B., Kentsis A., Sosnick T. R. D/H amide kinetic isotope effects reveal when hydrogen bonds form during protein folding. Nat Struct Biol. 2000 Jan;7(1):62–71. doi: 10.1038/71265. [DOI] [PubMed] [Google Scholar]
- Krantz Bryan A., Srivastava Alok K., Nauli Sehat, Baker David, Sauer Robert T., Sosnick Tobin R. Understanding protein hydrogen bond formation with kinetic H/D amide isotope effects. Nat Struct Biol. 2002 Jun;9(6):458–463. doi: 10.1038/nsb794. [DOI] [PubMed] [Google Scholar]
- Makhatadze G. I., Privalov P. L. Energetics of protein structure. Adv Protein Chem. 1995;47:307–425. doi: 10.1016/s0065-3233(08)60548-3. [DOI] [PubMed] [Google Scholar]
- Petrey D., Honig B. Free energy determinants of tertiary structure and the evaluation of protein models. Protein Sci. 2000 Nov;9(11):2181–2191. doi: 10.1110/ps.9.11.2181. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Prusiner S. B. Prions. Proc Natl Acad Sci U S A. 1998 Nov 10;95(23):13363–13383. doi: 10.1073/pnas.95.23.13363. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Shindyalov I. N., Bourne P. E. Protein structure alignment by incremental combinatorial extension (CE) of the optimal path. Protein Eng. 1998 Sep;11(9):739–747. doi: 10.1093/protein/11.9.739. [DOI] [PubMed] [Google Scholar]
- Vila J. A., Ripoll D. R., Scheraga H. A. Physical reasons for the unusual alpha-helix stabilization afforded by charged or neutral polar residues in alanine-rich peptides. Proc Natl Acad Sci U S A. 2000 Nov 21;97(24):13075–13079. doi: 10.1073/pnas.240455797. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Warshel A., Papazyan A. Electrostatic effects in macromolecules: fundamental concepts and practical modeling. Curr Opin Struct Biol. 1998 Apr;8(2):211–217. doi: 10.1016/s0959-440x(98)80041-9. [DOI] [PubMed] [Google Scholar]