Co-evolution of interacting proteins through non-contacting and non-specific mutations.

ABSTRACT: Proteins often accumulate neutral mutations that do not affect current functions but can profoundly influence future mutational possibilities and functions. Understanding such hidden potential has major implications for protein design and evolutionary forecasting but has been limited by a lack of systematic efforts to identify potentiating mutations. Here, through the comprehensive analysis of a bacterial toxin-antitoxin system, we identified all possible single substitutions in the toxin that enable it to tolerate otherwise interface-disrupting mutations in its antitoxin. Strikingly, the majority of enabling mutations in the toxin do not contact and promote tolerance non-specifically to many different antitoxin mutations, despite covariation in homologues occurring primarily between speci

SUBMITTER: Ding D 

PROVIDER: S-EPMC9090974 | biostudies-literature | 2022 May

REPOSITORIES: biostudies-literature