{Reference Type}: Journal Article
{Title}: Fast myosin binding protein C knockout in skeletal muscle alters length-dependent activation and myofilament structure.
{Author}: Hessel AL;Kuehn MN;Han SW;Ma W;Irving TC;Momb BA;Song T;Sadayappan S;Linke WA;Palmer BM;
{Journal}: Commun Biol
{Volume}: 7
{Issue}: 1
{Year}: 2024 May 27
{Factor}: 6.548
{DOI}: 10.1038/s42003-024-06265-8
{Abstract}: 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.