Institution: | aPathology Discipline, School of Medical Science and Bosch Institute, University of Sydney, NSW 2006, Australia bInstitute of Molecular Biophysics, Florida State University, Tallahassee, FL 32306, USA cDepartment of Chemistry and Biomolecular Sciences, Macquarie University, NSW 2109, Australia |
Abstract: | Myosin binding protein C (MyBPC) is a sarcomeric protein whose role in sarcomere structure and regulation of contraction is currently under investigation. It is a member of the immunoglobulin superfamily and is found in the C-zone of the A-band of the sarcomere. The elongated structure of MyBPC is composed of a series of immunoglobulin and fibronectin domains, with the C-terminal domains binding to the myosin thick filament and the N-terminal domains interacting with the myosin subfragment-2 (S2) neck region and possibly the actin thin filament. The functions of MyBPC are to stabilise the sarcomere structure and to regulate contraction. When phosphorylated near its N-terminus, MyBPC no longer binds myosin-S2, causing an increase in the ordering of the myosin heads, ATPase activity, Fmax and Ca2+ sensitivity of contraction. Mutations in MyBPC have been found to cause familial hypertrophic cardiomyopathy (FHC) and changes in MyBPC phosphorylation have been linked to cardiac ischaemia-reperfusion injury. |