Binding interface change and cryptic variation in the evolution of protein-protein interactions

BMC Evolutionary Biology

Research Article

David L. Robertson¹  Simon C. Lovell¹  Simon G. Williams²  David Talavera²  Ryan M. Ames³ 

[1] Computational and Evolutionary Biology, Faculty of Life Sciences, University of Manchester, Oxford Road, M13 9PT, Manchester, UK;Computational and Evolutionary Biology, Faculty of Life Sciences, University of Manchester, Oxford Road, M13 9PT, Manchester, UK;Current address: Institute of Cardiovascular Sciences, Faculty of Medical and Human Sciences, University of Manchester, Oxford Road, M13 9PT, Manchester, UK;Computational and Evolutionary Biology, Faculty of Life Sciences, University of Manchester, Oxford Road, M13 9PT, Manchester, UK;Current address: Wellcome Trust Centre for Biomedical Modelling and Analysis, University of Exeter, RILD Level 3, EX2 5DW, Exeter, UK;

关键词: Protein-protein interactions;    Gene duplication;    Evolution;    Protein complexes;    Protein structure;   

DOI  :  10.1186/s12862-016-0608-1

 received in 2015-06-25, accepted in 2016-02-02,  发布年份 2016

来源: Springer

【 摘 要 】

BackgroundPhysical interactions between proteins are essential for almost all biological functions and systems. To understand the evolution of function it is therefore important to understand the evolution of molecular interactions. Of key importance is the evolution of binding specificity, the set of interactions made by a protein, since change in specificity can lead to “rewiring” of interaction networks. Unfortunately, the interfaces through which proteins interact are complex, typically containing many amino-acid residues that collectively must contribute to binding specificity as well as binding affinity, structural integrity of the interface and solubility in the unbound state.ResultsIn order to study the relationship between interface composition and binding specificity, we make use of paralogous pairs of yeast proteins. Immediately after duplication these paralogues will have identical sequences and protein products that make an identical set of interactions. As the sequences diverge, we can correlate amino-acid change in the interface with any change in the specificity of binding. We show that change in interface regions correlates only weakly with change in specificity, and many variants in interfaces are functionally equivalent. We show that many of the residue replacements within interfaces are silent with respect to their contribution to binding specificity.ConclusionsWe conclude that such functionally-equivalent change has the potential to contribute to evolutionary plasticity in interfaces by creating cryptic variation, which in turn may provide the raw material for functional innovation and coevolution.

【 授权许可】

CC BY   
© Ames et al. 2016