%0 Journal Article
%T Fast myosin binding protein C knockout in skeletal muscle alters length-dependent activation and myofilament structure.
%A Hessel AL
%A Kuehn MN
%A Han SW
%A Ma W
%A Irving TC
%A Momb BA
%A Song T
%A Sadayappan S
%A Linke WA
%A Palmer BM
%J Commun Biol
%V 7
%N 1
%D 2024 May 27
%M 38802450
%F 6.548
%R 10.1038/s42003-024-06265-8
%X 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.