Structural destabilization of tropomyosin induced by the cardiomyopathy-linked mutation R21H.

ABSTRACT: The missense mutation R21H in striated muscle tropomyosin is associated with hypertrophic cardiomyopathy, a genetic cardiac disease and a leading cause of sudden cardiac death in young people. Tropomyosin adopts conformation of a coiled coil which is critical for regulation of muscle contraction. In this study, we investigated the effects of the R21H mutation on the coiled-coil structure of tropomyosin and its interactions with its binding partners, tropomodulin and leiomodin. Using circular dichroism and isothermal titration calorimetry, we found that the mutation profoundly destabilized the structural integrity of αTM1a_1-28 Zip, a chimeric peptide containing the first 28 residues of tropomyosin. The mutated αTM1a_1-28 Zip was still able to interact with tropomodulin

SUBMITTER: Ly T 

PROVIDER: S-EPMC5775174 | biostudies-literature | 2018 Feb

REPOSITORIES: biostudies-literature