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

Ames, R. M., Talavera, D., Williams, S. G., Robertson, D. L. and Lovell, S. C. (2016) Binding interface change and cryptic variation in the evolution of protein-protein interactions. BMC Evolutionary Biology, 16, 40. (doi: 10.1186/s12862-016-0608-1) (PMID:26892785) (PMCID:PMC4758157)

Abstract

Background: Physical 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. Results: In 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. Conclusions: We 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.

• Item Type: Articles
• Additional Information: This work was funded by BBSRC grant number BB/I020489/1 and generously supported by the Wellcome Trust Institutional Strategic Support Award (WT105618MA).
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Robertson, Professor David
• Authors: Ames, R. M., Talavera, D., Williams, S. G., Robertson, D. L., and Lovell, S. C.
• College/School: College of Medical Veterinary and Life Sciences > School of Infection & Immunity; College of Medical Veterinary and Life Sciences > School of Infection & Immunity > Centre for Virus Research
• Journal Name: BMC Evolutionary Biology
• Publisher: BioMed Central
• ISSN: 1471-2148
• ISSN (Online): 1471-2148
• Copyright Holders: Copyright © 2016 Ames et al.
• First Published: First published in BMC Evolutionary Biology 16: 40
• Publisher Policy: Reproduced under a Creative Commons License