Tuning the human heart molecular motors by myosin light chains.
Cardiac contraction is triggered by the cyclic interaction of the "molecular motor" protein myosin with the actin filament, consuming ATP as the energy source to produce tension or shortening. The myosin heavy chain (MHC) contains the actin- and ATP-binding sites and represents the molecular motor of muscle contraction. This review describes the various subunits of human heart myosin in health and disease and discusses their functions. Two different MHC genes (alpha and beta) with distinct biochemical features are expressed in the human heart. Alpha-MHC confers a higher ATPase activity and higher shortening velocity to the heart than beta-MHC. Motor function is regulated by myosin light chain (MLC) isoforms. Expression of the atrial MLC-1 isoform in the hypertrophied human ventricle increases cross-bridge cycling and contractility. It is suggested that MLC-1 acts as a MHC/actin tether. Weakening of this tether increases myosin function. MLC-2 slows the rate of tension development of myosin. This relative inhibition is relieved upon phosphorylation of the MLC-2 perhaps caused by "swing-out" of cross-bridges from the myosin filament. Mutations in all ventricular myosin subunits have been found in patients with hypertrophic cardiomyopathy.
Morano
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Max Delbrück Center for Molecular Medicine, Berlin-Buch, Germany. imorano@mdc-berlin.de
D000199:Actins / Q000378:metabolism; D000595:Amino Acid Sequence; D000818:Animals; D024722:Cardiac Myosins; D006321:Heart / Q000502:physiology*; D006801:Humans; D008954:Models, Biological; D008958:Models, Molecular; D008969:Molecular Sequence Data; D018482:Muscle, Skeletal / Q000378:metabolism; D009154:Mutation; D009200:Myocardial Contraction / Q000502:physiology*; D009206:Myocardium / Q000378:metabolism*; D018995:Myosin Heavy Chains / Q000502:physiology; D018994:Myosin Light Chains / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D010766:Phosphorylation; D020033:Protein Isoforms
D000199:Actins; D018994:Myosin Light Chains; D020033:Protein Isoforms; C107184:myosin light chain 2; D024722:Cardiac Myosins; D018995:Myosin Heavy Chains