DOI: 10.1073/pnas.95.9.4976. How evolution makes proteins fold quickly

How evolution makes proteins fold quickly

10.1073/pnas.95.9.4976

Crossref journal-article

Proceedings of the National Academy of Sciences

Proceedings of the National Academy of Sciences (341)

Abstract

Sequences of fast-folding model proteins (48 residues long on a cubic lattice) were generated by an evolution-like selection toward fast folding. We find that fast-folding proteins exhibit a specific folding mechanism in which all transition state conformations share a smaller subset of common contacts (folding nucleus). Acceleration of folding was accompanied by dramatic strengthening of interactions in the folding nucleus whereas average energy of nonnucleus interactions remained largely unchanged. Furthermore, the residues involved in the nucleus are the most conserved ones within families of evolved sequences. Our results imply that for each protein structure there is a small number of conserved positions that are key determinants of fast folding into that structure. This conjecture was tested on two protein superfamilies: the first having the classical monophosphate binding fold (CMBF; 98 families) and the second having type-III repeat fold (47 families). For each superfamily, we discovered a few positions that exhibit very strong and statistically significant “conservatism of conservatism”—amino acids in those positions are conserved within every family whereas the actual types of amino acids varied from family to family. Those amino acids are in spatial contact with each other. The experimental data of Serrano and coworkers [Lopez-Hernandez, E. & Serrano, L. (1996) Fold. Des. (London) 1, 43–55]. for one of the proteins of the CMBF superfamily (CheY) show that residues identified this way indeed belong to the folding nucleus. Further analysis revealed deep connections between nucleation in CMBF proteins and their function.

Bibliography

Mirny, L. A., Abkevich, V. I., & Shakhnovich, E. I. (1998). How evolution makes proteins fold quickly. Proceedings of the National Academy of Sciences, 95(9), 4976â4981.

Authors 3

Leonid A. Mirny (first)
Victor I. Abkevich (additional)
Eugene I. Shakhnovich (additional)

References 30 Referenced 150

10.1103/PhysRevLett.72.3907
10.1016/S0959-440X(97)80005-X
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L Holm, C Sander Nucleic Acids Res 22, 3600–3609 (1994). / Nucleic Acids Res by Holm L (1994)
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W Feller An Introduction to Probability Theory and its Applications (Wiley, New York, 1970). / An Introduction to Probability Theory and its Applications by Feller W (1970)
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Ptitsyn O. (1998) J. Mol. Biol. in press.
10.1006/jmbi.1997.1178

Dates

Type	When
Created	23 years, 1 month ago (July 26, 2002, 10:31 a.m.)
Deposited	3 years, 4 months ago (April 13, 2022, 4:19 p.m.)
Indexed	1 month, 4 weeks ago (June 30, 2025, 4:02 p.m.)
Issued	27 years, 4 months ago (April 28, 1998)
Published	27 years, 4 months ago (April 28, 1998)
Published Online	27 years, 4 months ago (April 28, 1998)
Published Print	27 years, 4 months ago (April 28, 1998)

Funders 0

None

BibTeX

@article{Mirny_1998, title={How evolution makes proteins fold quickly}, volume={95}, ISSN={1091-6490}, url={http://dx.doi.org/10.1073/pnas.95.9.4976}, DOI={10.1073/pnas.95.9.4976}, number={9}, journal={Proceedings of the National Academy of Sciences}, publisher={Proceedings of the National Academy of Sciences}, author={Mirny, Leonid A. and Abkevich, Victor I. and Shakhnovich, Eugene I.}, year={1998}, month=apr, pages={4976–4981} }

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