Key result
Skeletal and cardiac muscle thick filaments share conserved architecture, differing primarily in MyBP-C domain positioning.
Why the study?
The similarity and differences between vertebrate skeletal and cardiac muscle myosin filaments were not fully characterized at high resolution.
High-resolution structural analysis demonstrates that vertebrate skeletal and cardiac thick filaments share a highly conserved architecture, providing a structural basis for understanding muscle-specific regulatory mechanisms.
Conserved thick filament structures across species may guide mechanistic models; leaves open whether MyBP-C positioning differences modulate cardiac versus skeletal function.
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.
No takes yet. Share an insight, caveat, or question.
Tilko et al. (2026) studied Muscle structure (basic science). Cryo-electron microscopy and 3D reconstruction vs. Cardiac muscle thick filaments was evaluated on Subnanometer structural resolution of the C-zone of native skeletal myosin filaments.
Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context: