Activation And Inhibition Of Cardiac Thin Filaments By Single And Multiple Domains Constructs Of Human Cardiac Myosin Binding Protein-C (Cmybp-C) At Low Calcium

We have previously shown that the C1 domain of human cardiac myosin binding protein-C (c-MyBP-C) produces a biphasic regulation of cardiac thin filaments at low calcium concentrations. Increasing [C1] first produces activation followed by inhibition of myosin-S1 ATP hydrolysis by cardiac thin filaments at higher [C1]. In contrast, domains C0 and C2 only inhibit and do not activate ATP hydrolysis at any concentration. N’-terminal proteins containing the C1 domain along with C0 or C2 (e.g., C0-PA-C1, C1-M-C2 and C0-PA-C1-M-C2) show a similar pattern of activation and inhibition of ATP hydrolysis at low calcium concentration as the C1 domain alone, but the concentrations required for maximum activation and inhibition are ∼10 fold lower than required using C1 alone.