Cardiac myosin binding protein C

Myosin binding protein C (MyBP-C) is one of a group of myosin binding prote ins 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 t itin binding sites at the C terminus of the molecule in all 3 of the isofor ms (slow skeletal, fast skeletal, and cardiac). The cardiac isoform also in cludes a series of residues that contain 3 phosphorylatable sites and an ad ditional immunoglobulin module at the N terminus that are not present in sk eletal isoforms. The following 2 major functions of MyBP-C have been sugges ted: (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, re gulation of contraction through phosphorylation. The first is supported by the demonstrated effect of MyBP-C on the packing of myosin in the thick fil ament, the coincidence of appearance of sarcomeres and MyBP-C during myofib rillogenesis, and the defective formation of sarcomeres when the titin and/ or myosin binding sites of MyBP-C are missing. The second is supported by t he specific phosphorylation sites in cardiac MyBP-C, the presence in the th ick filament of an enzyme specific for MyBP-C phosphorylation, the alterati on of thick filament structure by MyBP-C phosphorylation, and the accompani ment of MyBP-C phosphorylation with all major physiological mechanisms of m odulation of inotropy in the heart.