Distortion of the Actin A-Triad Results in Contractile Disinhibition and Cardiomyopathy.

ABSTRACT: Striated muscle contraction is regulated by the movement of tropomyosin over the thin filament surface, which blocks or exposes myosin binding sites on actin. Findings suggest that electrostatic contacts, particularly those between K326, K328, and R147 on actin and tropomyosin, establish an energetically favorable F-actin-tropomyosin configuration, with tropomyosin positioned in a location that impedes actomyosin associations and promotes relaxation. Here, we provide data that directly support a vital role for these actin residues, termed the A-triad, in tropomyosin positioning in intact functioning muscle. By examining the effects of an A295S α-cardiac actin hypertrophic cardiomyopathy-causing mutation, over a range of increasingly complex in silico, in vitro, and in vivo Drosophila muscl

SUBMITTER: Viswanathan MC 

PROVIDER: S-EPMC5902318 | biostudies-literature | 2017 Sep

REPOSITORIES: biostudies-literature