| First Author | Hessel AL | Year | 2024 |
| Journal | Commun Biol | Volume | 7 |
| Issue | 1 | Pages | 648 |
| PubMed ID | 38802450 | Mgi Jnum | J:348851 |
| Mgi Id | MGI:7644239 | Doi | 10.1038/s42003-024-06265-8 |
| Citation | Hessel AL, et al. (2024) Fast myosin binding protein C knockout in skeletal muscle alters length-dependent activation and myofilament structure. Commun Biol 7(1):648 |
| abstractText | In striated muscle, the sarcomeric protein myosin-binding protein-C (MyBP-C) is bound to the myosin thick filament and is predicted to stabilize myosin heads in a docked position against the thick filament, which limits crossbridge formation. Here, we use the homozygous Mybpc2 knockout (C2(-/-)) mouse line to remove the fast-isoform MyBP-C from fast skeletal muscle and then conduct mechanical functional studies in parallel with small-angle X-ray diffraction to evaluate the myofilament structure. We report that C2(-/-) fibers present deficits in force production and calcium sensitivity. Structurally, passive C2(-/-) fibers present altered sarcomere length-independent and -dependent regulation of myosin head conformations, with a shift of myosin heads towards actin. At shorter sarcomere lengths, the thin filament is axially extended in C2(-/-), which we hypothesize is due to increased numbers of low-level crossbridges. These findings provide testable mechanisms to explain the etiology of debilitating diseases associated with MyBP-C. |
