Evolutionary Optimization of Protein Folding
Cédric Debès, Minglei Wang, Gustavo Caetano-Anollés, Frauke Gräter
Nature has come up with an enormous variety of protein three-dimensional structures, each of which is thought to be optimized for its specific function. A fundamental biological endeavor is to uncover the driving evolutionary forces for discovering and optimizing new folds. A long-standing hypothesis is that fold evolution obeys constraints to properly fold into native structure. We here test this hypothesis by analyzing trends of proteins to fold fast during evolution. Using phylogenomic and structural analyses, we observe an overall decrease in folding times between 3.8 and 1.5 billion years ago, which can be interpreted as an evolutionary optimization for rapid folding. This trend towards fast folding probably resulted in manifold advantages, including high protein accessibility for the cell and a reduction of protein aggregation during misfolding.
Citation: Debès C, Wang M, Caetano-Anollés G, Gräter F (2013) Evolutionary Optimization of Protein Folding. PLoS Comput Biol 9(1): e1002861. doi:10.1371/journal.pcbi.1002861
Editor: Ruth Nussinov, National Cancer Institute, United States of America and Tel Aviv University, Israel
Received: July 3, 2012; Accepted: November 9, 2012; Published: January 17, 2013
Copyright: © 2013 Debès et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Funding: This study was supported by the National Science Foundation (Grant MCB-0749836 to GCA) and the Klaus Tschira Foundation. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Competing interests: The authors have declared that no competing interests exist.
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