UMMS Affiliation

Department of Physiology

Publication Date

1996-12-15

Document Type

Article

Subjects

Actins; Adenosine Triphosphatases; Baculoviridae; Binding Sites; Cardiomyopathies; Cloning, Molecular; DNA Primers; DNA, Complementary; Electrophoresis, Polyacrylamide Gel; Gene Expression; Genetic Vectors; Humans; Models, Molecular; Myocardium; Myosin Light Chains; Myosins; Point Mutation; Recombinant Proteins; Structure-Activity Relationship

Disciplines

Physiology

Abstract

More than 30 missense mutations in the beta-cardiac myosin heavy chain gene have been shown to be responsible for familial hypertrophic cardiomyopathy. To clarify the effects of these point mutations on myosin motor function, we expressed wild-type and mutant human beta-cardiac myosin heavy chains in insect cells with human cardiac light chains. The wild-type myosin was well purified with similar enzymatic and motor activities to those of the naturally isolated V3 cardiac myosin. Arg249-->Gln and Arg453-->Cys mutations resulted in decreased actin translocating activity (61 and 23% of the wild-type, respectively) with decreased intrinsic ATPase activity. Arg403-->Gln mutation greatly decreased actin translocating activity (27% of wild type) with a 3.3-fold increased dissociation constant for actin, while intrinsic ATPase activity was unchanged. Val606-->Met mutation only mildly affected the actin translocating activity as well as ATPase activity of myosin. The degree of deterioration by each mutation was closely correlated with the prognosis of the affected kindreds, indicating that myosin dysfunction caused by the point mutations is responsible for the pathogenesis of the disease. Structure/function relationship of myosin is discussed.

DOI of Published Version

10.1172/JCI119115

Source

J Clin Invest. 1996 Dec 15;98(12):2866-73. Link to article on publisher's site

Journal/Book/Conference Title

The Journal of clinical investigation

Related Resources

Link to Article in PubMed

PubMed ID

8981935

Included in

Physiology Commons

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