Evolving New Protein-Protein Interaction Specificity through Promiscuous Intermediates
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Laub_Evolving new.pdf
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Author(s)
Herrou, Julien
Crosson, Sean
Aakre, Christopher David
Phung, Tuyen N.
Perchuk, Barrett
Laub, Michael T
Date Issued
October 2015
Journal
Cell
Publisher
Elsevier
Citation
Aakre, Christopher D. et al. “Evolving New Protein-Protein Interaction Specificity through Promiscuous Intermediates.” Cell 163.3 (2015): 594–606.
Version
Author's final manuscript
Abstract
Interacting proteins typically coevolve, and the identification of coevolving amino acids can pinpoint residues required for interaction specificity. This approach often assumes that an interface-disrupting mutation in one protein drives selection of a compensatory mutation in its partner during evolution. However, this model requires a non-functional intermediate state prior to the compensatory change. Alternatively, a mutation in one protein could first broaden its specificity, allowing changes in its partner, followed by a specificity-restricting mutation. Using bacterial toxin-antitoxin systems, we demonstrate the plausibility of this second, promiscuity-based model. By screening large libraries of interface mutants, we show that toxins and antitoxins with high specificity are frequently connected in sequence space to more promiscuous variants that can serve as intermediates during a reprogramming of interaction specificity. We propose that the abundance of promiscuous variants promotes the expansion and diversification of toxin-antitoxin systems and other paralogous protein families during evolution.
MIT Department
Massachusetts Institute of Technology. Department of Biology
Terms of Use
Creative Commons Attribution-NonCommercial-NoDerivs License
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DOI of Published Version
https://doi.org/10.1016/j.cell.2015.09.055
