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

alpha-Tropomyosin (cam) is central to Ca2+-regulation of cardiac muscle contraction. The familial hypertrophic cardiomyopathy mutation alpha Tm E180G enhances Ca2+-sensitivity in functional assays. To investigate the molecular basis, we imaged single molecules of human cardiac alpha Tm E180G by direct probe atomic force microscopy. Analyses of tangent angles along molecular contours yielded persistence length corresponding to similar 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. (C) 2012 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.