Variable Autoinhibition among Deafness-Associated Variants of Diaphanous 1 (DIAPH1).

ABSTRACT: One of the earliest mapped human deafness genes, DIAPH1, encodes the formin DIAPH1. To date, at least three distinct mutations in the C-terminal domains and two additional mutations in the N-terminal region are associated with autosomal dominant hearing loss. The underlying molecular mechanisms are not known, and the role of formins in the inner ear is not well understood. In this study, we use biochemical assays to test the hypotheses that autoinhibition and/or actin assembly activities are disrupted by DFNA1 mutations. Our results indicate that C-terminal mutant forms of DIAPH1 are functional in vitro and promote actin filament assembly. Similarly, N-terminal mutants are well-folded and have quaternary structures and thermal stabilities similar to those of the wild-type (WT

SUBMITTER: Lakha R 

PROVIDER: S-EPMC8447886 | biostudies-literature | 2021 Jul

REPOSITORIES: biostudies-literature