MyBP-C was discovered as a myosin binding protein in 1970, but its structural organization and function have remained elusive. There is currently renewed interest in this protein because in cardiac muscle it is known to modulate contraction, and it has been implicated in inherited heart and skeletal muscle diseases. Early antibody labeling studies showed that MyBP-C is located in a series of stripes (one at every third level of myosin heads) in each half of the A-band (left figure), but its 3D organization remained unknown. We have recently collaborated with Dr. Pradeep Luther (Imperial College, London) who carried out electron tomographic observations of especially well preserved muscle sections prepared in our lab. The tomograms show that MyBP-C, far from being confined to the thick filament surface, actually extends out to the thin filaments, to which it attaches (Luther et al., 2011). This is seen as the extensive disk of density (pink) in right figure below. This is the first demonstration that MyBP-C-actin interactions previously observed in vitro may have relevance in intact muscle. Bridging between myosin and actin would provide a physical basis for understanding MyBP-C’s ability to modulate contraction. For details of MyBP-C’s interaction with actin see Interaction of MyBP-C with Thin Filaments.
Organization of MyBP-C in striated muscle. Left: rabbit muscle labeled with antibodies to MyBP-C, showing periodic organization in each half of the A-band. Right: Part of tomographic reconstruction of thick filament, showing MyBP-C extending from the thick filament backbone (grey) as a disk-like cloud of density (pink; Luther et al., 2011). Orange shows C-terminal MyBP-C domains on thick filament surface (Zoghbi et al., 2008).