Altered Pore Composition and Flexibility in a Deafness-Associated TMC1 Variant: Insights from Molecular Dynamics Simulations.

ABSTRACT: Transmembrane channel-like protein 1 (TMC1) forms the pore of the mechanotransduction channel in cochlear and vestibular hair cells, converting mechanical stimuli from sound and head movements into electrochemical signals. Recent evidence supports a dimeric structure for TMC1, with each monomer harboring an independent ion-conducting pore. The p.(M654V) variant, in which methionine 654 is substituted with valine, is associated with non-syndromic autosomal recessive deafness. In the present work, we used molecular dynamics (MD) simulations to compare the structural and biophysical properties of the wild-type and M654V-TMC1 variants, providing atomistic-level insights into subtle alterations in the mechanotransduction system. Our analysis reveals specific alterations in pore size, lipid comp

SUBMITTER: Zamboni D 

PROVIDER: S-EPMC12715761 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature