Epistasis shapes the fitness landscape of an allosteric specificity switch.

ABSTRACT: Epistasis is a major determinant in the emergence of novel protein function. In allosteric proteins, direct interactions between inducer-binding mutations propagate through the allosteric network, manifesting as epistasis at the level of biological function. Elucidating this relationship between local interactions and their global effects is essential to understanding evolution of allosteric proteins. We integrate computational design, structural and biophysical analysis to characterize the emergence of novel inducer specificity in an allosteric transcription factor. Adaptive landscapes of different inducers of the designed mutant show that a few strong epistatic interactions constrain the number of viable sequence pathways, revealing ridges in the fitness landscape leading to new specific

SUBMITTER: Nishikawa KK 

PROVIDER: S-EPMC8455584 | biostudies-literature | 2021 Sep

REPOSITORIES: biostudies-literature