Evolutionary selection of proteins with two folds.

ABSTRACT: Although most globular proteins fold into a single stable structure, an increasing number have been shown to remodel their secondary and tertiary structures in response to cellular stimuli. State-of-the-art algorithms predict that these fold-switching proteins adopt only one stable structure, missing their functionally critical alternative folds. Why these algorithms predict a single fold is unclear, but all of them infer protein structure from coevolved amino acid pairs. Here, we hypothesize that coevolutionary signatures are being missed. Suspecting that single-fold variants could be masking these signatures, we developed an approach, called Alternative Contact Enhancement (ACE), to search both highly diverse protein superfamilies-composed of single-fold and fold-switching variants-and p

SUBMITTER: Schafer JW 

PROVIDER: S-EPMC10482954 | biostudies-literature | 2023 Sep

REPOSITORIES: biostudies-literature