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Familial hypertrophic cardiomyopathy related E180G mutation increases flexibility of human cardiac α‐tropomyosin
Author(s) -
Loong Campion K.P.,
Zhou Huan-Xiang,
Bryant Chase P.
Publication year - 2012
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/j.febslet.2012.08.005
Subject(s) - hypertrophic cardiomyopathy , tropomyosin , cardiac muscle , contraction (grammar) , medicine , cardiomyopathy , diastole , cardiac hypertrophy , cardiology , muscle hypertrophy , chemistry , biophysics , biology , heart failure , myosin , blood pressure
α‐Tropomyosin (αTm) is central to Ca 2+ ‐regulation of cardiac muscle contraction. The familial hypertrophic cardiomyopathy mutation αTm E180G enhances Ca 2+ ‐sensitivity in functional assays. To investigate the molecular basis, we imaged single molecules of human cardiac αTm 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.