Radial displacement of myosin cross-bridges in mouse myocardium due to ablation of myosin binding protein-C

Myosin binding protein-C (cMyBP-C) is a thick filament accessory protein, which in cardiac muscle functions to regulate the kinetics of cross-bridge interaction with actin; however, the underlying mechanism is not yet understood. To explore the structural basis for cMyBP-C function, we used synchrotron low-angle X-ray diffraction to measure interfilament lattice spacing and the equatorial intensity ratio, I-11/I-10, in skinned myocardial preparations isolated from wild-type (WT) and cMyBP-C null (cMyBP-C-/-). In relaxed myocardium, ablation of cMyBP-C appeared to result in radial displacement of cross-bridges away from the thick filaments, as there was a significant increase (similar to 30%) in the I-11/I-10 ratio for cMyBP-C-/- (0.37 +/- 0.03) myocardium as compared to WT (0.28 +/- 0.01). While lattice spacing tended to be greater incMyBP-C-/- myocardium (44.18 +/- 0.68 nm) when compared to WT (42.95 +/- 0.43 nm), the difference was not statistically significant. Furthermore, liquid-like disorder in the myofilament lattice was significantly greater (similar to 40% greater) in cMyBP-C myocardium. as compared to WT. These results are consistent with our working hypothesis that cMyBP-C normally acts to tether myosin cross-bridges nearer to the thick filament backbone, thereby reducing the likelihood of cross-bridge binding to actin and limiting cooperative activation of the thin filament. Published by Elsevier Ltd.