Uncovering the basis of protein-protein interaction specificity with a combinatorially complete library.

ABSTRACT: Protein-protein interaction specificity is often encoded at the primary sequence level. However, the contributions of individual residues to specificity are usually poorly understood and often obscured by mutational robustness, sequence degeneracy, and epistasis. Using bacterial toxin-antitoxin systems as a model, we screened a combinatorially complete library of antitoxin variants at three key positions against two toxins. This library enabled us to measure the effect of individual substitutions on specificity in hundreds of genetic backgrounds. These distributions allow inferences about the general nature of interface residues in promoting specificity. We find that positive and negative contributions to specificity are neither inherently coupled nor mutually exclusive. Further, a wild-ty

SUBMITTER: Lite TV 

PROVIDER: S-EPMC7669267 | biostudies-literature | 2020 Oct

REPOSITORIES: biostudies-literature