Physical origins of protein superfamilies

JOURNAL OF MOLECULAR BIOLOGY

卷:357

Article

Zeldovich, KB ; Berezovsky, IN ; Shakhnovich, EI

关键词: protein evolution;    designability;    stability;    superfamilies;   

DOI  :  10.1016/j.jmb.2006.01.081

来源: Elsevier

【 摘 要 】

In this work, we discovered a fundamental connection between selection for protein stability and emergence of preferred structures of proteins. Using a standard exact three-dimensional lattice model we evolve sequences starting from random ones and determine the exact native structure after each mutation. Acceptance of mutations is biased to select for stable proteins. We found that certain structures, wonderfolds, are independently discovered numerous times as native states of stable proteins in many unrelated runs of selection. The strong dependence of lattice fold usage on the structural determinant of designability quantitatively reproduces uneven fold usage in natural proteins. Diversity of sequences that fold into wonderfold structures gives rise to superfamilies, i.e. sets of dissimilar sequences that fold into the same or very similar structures. The present work establishes a model of pre-biotic structure selection, which identifies dominant structural patterns emerging upon optimization of proteins for survival in a hot environment. Convergently discovered pre-biotic initial superfamilies with wonderfold structures could have served as a seed for subsequent biological evolution involving gene duplications and divergence. (c) 2006 Elsevier Ltd. All rights reserved.

【 授权许可】

Free