Exploring force-driven stochastic folding dynamics in mechano-responsive proteins and implications in phenotypic variation.

ABSTRACT: Single-point mutations are pivotal in molecular zoology, shaping functions and influencing genetic diversity and evolution. Here we study three such genetic variants of a mechano-responsive protein, cadherin-23, that uphold the structural integrity of the protein, but showcase distinct genotypes and phenotypes. The variants exhibit subtle differences in transient intra-domain interactions, which in turn affect the anti-correlated motions among the constituent β-strands. In nature, the variants experience declining functions with aging at different rates. We expose these variants to constant and oscillatory forces using magnetic tweezer, and measure variations in stochastic folding dynamics. All variants exhibit multiple microstates under force. However, the protein variant with higher numb

SUBMITTER: Saha P 

PROVIDER: S-EPMC11763006 | biostudies-literature | 2025 Jan

REPOSITORIES: biostudies-literature