A contact-based analysis of local energetic frustration dynamics identifies key residues enabling RfaH fold-switch.

ABSTRACT: Fold-switching enables metamorphic proteins to reversibly interconvert between two highly dissimilar native states to regulate their protein functions. While about 100 proteins have been identified to undergo fold-switching, unveiling the key residues behind this mechanism for each protein remains challenging. Reasoning that fold-switching in proteins is driven by dynamic changes in local energetic frustration, we combined fold-switching simulations generated using simplified structure-based models with frustration analysis to identify key residues involved in this process based on the change in the density of minimally frustrated contacts during refolding. Using this approach to analyze the fold-switch of the bacterial transcription factor RfaH, we identified 20 residues that significantl

SUBMITTER: Gonzalez-Higueras J 

PROVIDER: S-EPMC11425668 | biostudies-literature | 2024 Oct

REPOSITORIES: biostudies-literature