Evolving new protein-protein interaction specificity through promiscuous intermediates.

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 frequent

SUBMITTER: Aakre CD 

PROVIDER: S-EPMC4623991 | biostudies-literature | 2015 Oct

REPOSITORIES: biostudies-literature