Myosin filaments of vertebrate skeletal and cardiac muscle are highly similar, but not identical

Striated muscles consist of two filament types, one based on actin, one based on myosin. All striated muscle actin filaments are highly similar. Invertebrate myosin filaments are heterogeneous; those of vertebrates are homogeneous. Mouse and human cardiac muscle myosin filaments are highly similar. How similar are they to those of skeletal muscle? Using Mavacamten for myosin head stabilization, we find the relaxed thick filaments of rabbit skeletal, human cardiac and mouse cardiac muscles are highly similar, differing primarily in the positioning of myosin binding protein C domains, C5-C7. In isolated cardiac thick filaments, C5-C7 lie along the filament backbone. In mouse and human cardiac myofibrils, C7 extends radially toward the thin filament. Here we show in isolated rabbit skeletal muscle thick filaments, C7 also extends outward but with C6 bending azimuthally to position C5 onto titin suggesting a thick filament architecture highly adaptable to multiple functions with relatively simple structural changes. The least understood muscle filament contains myosin. How similar are myosin filaments across muscle types and species? Here the authors show rabbit skeletal and human cardiac thick filaments are highly similar, demonstrating an architecture highly adaptable with simple structural changes