title: Familial hypertrophic cardiomyopathy related E180G mutation increases flexibility of human cardiac α-tropomyosin.
abstract: 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.
authors.affiliation: Department of Biological Science, The Florida State University, Tallahassee, FL 32306-4370, USA.
authors.forename: Campion K P
authors.initials: CK
authors.lastname: Loong
authors.forename: Huan-Xiang
authors.initials: HX
authors.lastname: Zhou
authors.forename: P Bryant
authors.initials: PB
authors.lastname: Chase
mesh_terms: D019943:Amino Acid Substitution; D002118:Calcium / Q000378:metabolism; D024741:Cardiomyopathy, Hypertrophic, Familial / Q000235:genetics* / Q000503:physiopathology; D006801:Humans; D018625:Microscopy, Atomic Force; D008955:Models, Cardiovascular; D008958:Models, Molecular; D050505:Mutant Proteins / Q000737:chemistry* / Q000235:genetics* / Q000502:physiology / Q000648:ultrastructure; D020125:Mutation, Missense; D009200:Myocardial Contraction / Q000235:genetics / Q000502:physiology; D011487:Protein Conformation; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000648:ultrastructure; D014335:Tropomyosin / Q000737:chemistry* / Q000235:genetics* / Q000502:physiology / Q000648:ultrastructure
chemical_list: D050505:Mutant Proteins; D011994:Recombinant Proteins; C490775:TPM1 protein, human; D014335:Tropomyosin; D002118:Calcium