Myosin binding protein C (MyBP-C) is a thick-filament protein that limits cross-bridge cycling rates and reduces myocyte power output. To investigate mechanisms by which MyBP-C affects contraction, we assessed effects of re-combinant N-terminal domains of cardiac MyBP-C (cMyBP-C) on contractile properties of permeabilized rat car-diac trabeculae. Here, we show that N-terminal fragments of cMyBP-C that contained the first three immunoglobulin domains of cMyBP-C (i.e., CO, Cl, and C2) plus the unique linker sequence termed the MyBP-C "motif or "m-do-main" increased Ca 2+ sensitivity of tension and increased rates of tension redevelopment (i.e., K trτ) at submaximal levels of Ca 2+. At concentrations >20 μM, recombinant proteins also activated force in the absence of Ca 2+ and in-hibited maximum Ca 2+-activated force. Recombinant proteins that lacked the combination of Cl and the motif did not affect contractile properties. These results suggest that the Cl domain plus the motif constitute a functional unit of MyBP-C that can activate the thin filament.
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