Familial hypertrophic cardiomyopathy related E180G mutation increases flexibility of human cardiac ?-tropomyosin.

ABSTRACT: ?-Tropomyosin (?Tm) is central to Ca(2+)-regulation of cardiac muscle contraction. The familial hypertrophic cardiomyopathy mutation ?Tm E180G enhances Ca(2+)-sensitivity in functional assays. To investigate the molecular basis, we imaged single molecules of human cardiac ?Tm E180G by direct probe atomic force microscopy. Analyses of tangent angles along molecular contours yielded persistence length corresponding to ~35% increase in flexibility compared to wild-type. Increased flexibility of the mutant was confirmed by fitting end-to-end length distributions to the worm-like chain model. This marked increase in flexibility can significantly impact systolic and possibly diastolic phases of cardiac contraction, ultimately leading to hypertrophy.

SUBMITTER: Loong CK 

PROVIDER: S-EPMC3455129 | biostudies-literature | 2012 Sep

REPOSITORIES: biostudies-literature