title: Mutations in either the essential or regulatory light chains of myosin are associated with a rare myopathy in human heart and skeletal muscle.
abstract: The muscle myosins and hexomeric proteins consisting of two heavy chains and two pairs of light chains, the latter called essential (ELC) and regulatory (RLC). The light chains stabilize the long alpha helical neck of the myosin head. Their function in striated muscle, however, is only partially understood. We report here the identification of distinct missense mutations in a skeletal/ventricular ELC and RLC, each of which are associated with a rare variant of cardiac hypertrophy as well as abnormal skeletal muscle. We show that myosin containing the mutant ELC has abnormal function, map the mutant residues on the three-dimensional structure of myosin and suggest that the mutations disrupt the stretch activation response of the cardiac papillary muscles.
authors.affiliation: Inherited Cardiac Diseases Section, NHLBI, NIH. Bethesda, Maryland 20892-1650, USA.
authors.forename: K
authors.initials: K
authors.lastname: Poetter
authors.forename: H
authors.initials: H
authors.lastname: Jiang
authors.forename: S
authors.initials: S
authors.lastname: Hassanzadeh
authors.forename: S R
authors.initials: SR
authors.lastname: Master
authors.forename: A
authors.initials: A
authors.lastname: Chang
authors.forename: M C
authors.initials: MC
authors.lastname: Dalakas
authors.forename: I
authors.initials: I
authors.lastname: Rayment
authors.forename: J R
authors.initials: JR
authors.lastname: Sellers
authors.forename: L
authors.initials: L
authors.lastname: Fananapazir
authors.forename: N D
authors.initials: ND
authors.lastname: Epstein
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002312:Cardiomyopathy, Hypertrophic / Q000235:genetics* / Q000378:metabolism; D002645:Chickens; D017931:DNA Primers; D005260:Female; D008040:Genetic Linkage; D006801:Humans; D008126:Lod Score; D008297:Male; D051379:Mice; D008961:Models, Structural; D008969:Molecular Sequence Data; D018482:Muscle, Skeletal / Q000378:metabolism*; D009135:Muscular Diseases / Q000235:genetics* / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism*; D018994:Myosin Light Chains / Q000737:chemistry / Q000235:genetics*; D009218:Myosins / Q000737:chemistry*; D010375:Pedigree; D017354:Point Mutation; D016133:Polymerase Chain Reaction; D018807:Polymorphism, Single-Stranded Conformational; D017433:Protein Structure, Secondary; D051381:Rats; D017386:Sequence Homology, Amino Acid; D018487:Ventricular Dysfunction, Left
chemical_list: D017931:DNA Primers; D018994:Myosin Light Chains; D009218:Myosins