Comparing cryo-EM structures of the vertebrate cardiac muscle thick filament.

The thick filaments of muscle carry the myosin motors that generate contraction by interacting with actin filaments. Despite decades of research, an atomic model of the vertebrate striated muscle thick filament has been lacking. Three cryo-EM thick filament structures from cardiac muscle have now been reported, revealing the organization of myosin heads in interacting-heads motifs (IHMs) on the thick filament surface, and a complex arrangement of myosin tails, titin, and myosin-binding protein C (MyBP-C) in the filament backbone. The three studies are complementary, coming from two species (mouse and human), two techniques (cryo-electron tomography and single particle cryo-EM), and from muscles treated or untreated with the myosin-stabilizing drug mavacamten. The structures are remarkably similar, agreeing on most elements of molecular organization but differing on the degree of stability of the IHMs and the organization of MyBP-C. The differences arise from the different techniques used and the observation of filaments within, or isolated from, the filament lattice.