Two Deafness-Causing Actin Mutations (DFNA20/26) Have Allosteric Effects on the Actin Structure.

ABSTRACT: Point mutations in γ-cytoplasmic actin have been shown to result in autosomal-dominant, nonsyndromic, early-onset deafness. Two mutations at the same site, K118M and K118N, provide a unique opportunity to compare the effects of two dissimilar amino acid substitutions that produce a similar phenotype in humans. K118 resides in a helix that runs from K113 to T126, and mutations that alter the position, dynamics, and/or biochemistry of this helix can result in a wide range of pathologies. Using a combination of computational and experimental studies, both employing yeast actin, we find that these mutations at K118 result in changes in the structure and dynamics of the DNase-I loop, alterations in the structure of the H73 loop as well as the side-chain orientations of W79 and W86, changes in n

SUBMITTER: Jepsen L 

PROVIDER: S-EPMC4968419 | biostudies-literature | 2016 Jul

REPOSITORIES: biostudies-literature