© 1999 American Heart Association, Inc.
Review |
Cardiac Myosin Binding Protein C
From the Department of Physiology, School of Medicine, University of Pennsylvania, Philadelphia, Pa.
Correspondence to Saul Winegrad, Department of Physiology, School of Medicine, University of Pennsylvania, Philadelphia, PA 19104-6085. E-mail bsg{at}mail.med.upenn.edu
Abstract—Myosin binding protein C (MyBP-C) is one of a group of myosin binding proteins that are present in the myofibrils of all striated muscle. The protein is found at 43-nm repeats along 7 to 9 transverse lines in a portion of the A band where crossbridges are found (C zone). MyBP-C contains myosin and titin binding sites at the C terminus of the molecule in all 3 of the isoforms (slow skeletal, fast skeletal, and cardiac). The cardiac isoform also includes a series of residues that contain 3 phosphorylatable sites and an additional immunoglobulin module at the N terminus that are not present in skeletal isoforms. The following 2 major functions of MyBP-C have been suggested: (1) a role in the formation of the sarcomeric myofibril as a result of binding to myosin and titin and (2) in the case of the cardiac isoform, regulation of contraction through phosphorylation. The first is supported by the demonstrated effect of MyBP-C on the packing of myosin in the thick filament, the coincidence of appearance of sarcomeres and MyBP-C during myofibrillogenesis, and the defective formation of sarcomeres when the titin and/or myosin binding sites of MyBP-C are missing. The second is supported by the specific phosphorylation sites in cardiac MyBP-C, the presence in the thick filament of an enzyme specific for MyBP-C phosphorylation, the alteration of thick filament structure by MyBP-C phosphorylation, and the accompaniment of MyBP-C phosphorylation with all major physiological mechanisms of modulation of inotropy in the heart.
Key Words: myosin binding protein C • heart • filament structure • force generation • regulation of contraction
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