Key result
HCM mutations along the myosin mesa may increase cardiac power by releasing MyBP-C inhibition.
Proposes a novel molecular mechanism for hypertrophic cardiomyopathy involving the myosin mesa and myosin-binding protein C.
May identify myosin-targeted HCM therapies; leaves open validation in models and trials.
No matter how many times one explores the structure of the myosin molecule, there is always something new to discover. Here, I describe the myosin mesa, a structural feature of the motor domain that has the characteristics of a binding domain for another protein, possibly myosin-binding protein C (MyBP-C). Interestingly, many well-known hypertrophic cardiomyopathy (HCM) mutations lie along this surface and may affect the putative interactions proposed here. A potential unifying hypothesis for the molecular basis of human hypertrophic cardiomyopathy is discussed here. It involves increased power output of the cardiac muscle as a result of HCM mutations causing the release of inhibition by myosin binding protein C.
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James A. Spudich (2015) studied this question. Hypertrophic cardiomyopathy mutations along the myosin mesa may increase cardiac muscle power output by releasing the inhibitory effect of myosin-binding protein C.
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