Functional effects of nemaline myopathy mutations on human skeletal alpha-actin.

ABSTRACT: Mutations in human alpha-skeletal actin have been implicated in causing congenital nemaline myopathy, a disease characterized histopathologically by nemaline bodies in skeletal muscle and manifested in the patient as skeletal muscle weakness. Here we investigate the functional effects of three severe nemaline myopathy mutations (V43F, A138P, and R183G) in human alpha-skeletal actin. Wild-type and mutant actins were expressed and purified from the baculovirus/insect cell expression system. The mutations are located in different subdomains of actin; Val-43 is located in a flexible loop of subdomain 2, Ala-138 is near a hydrophobic cleft in the "hinge" region between subdomains 1 and 3, and Arg-183 is near the nucleotide-binding site. None of the three mutations affected the folding of the ac

SUBMITTER: Miller BM 

PROVIDER: S-EPMC2443645 | biostudies-literature | 2008 Jul

REPOSITORIES: biostudies-literature