Myosin Binding Protein-C (MyBP-C)
MyBP-C is a striated muscle contractile protein, mutations to which have been linked to genetic forms of hypertrophic and dilated cardiomyopathies as well as skeletal muscle myopathies (i.e. distal arthrogryposis). MyBP-C is expressed as 3 isoforms; fast skeletal, slow skeletal, and cardiac. It’s an elongated protein with at least 10 globular domains (yellow structures). MyBP-C associates with the myosin thick filament at one end and both the myosin head region and actin at its other end.
Although MyBP-C affects actomyosin function, the molecular mechanism by which this occurs is far from certain, with multiple models proposed for its action. The specific model depends on MyBP-C’s binding partner. For example, by binding to the myosin head region, MyBP-C may limit myosin’s interaction with actin and maintain myosin in a super-relaxed state. Alternatively, MyBP-C may bind to actin and act as an internal load to shortening or activate the thin filament in a calcium-independent manner.
Our laboratory uses molecular biophysics to unravel the key interactions between MyBP-C and both actin and myosin that allow this unique protein to modulate actomyosin function in the heart and in skeletal muscles.