Fast myosin binding protein C knockout in skeletal muscle alters length-dependent activation and myofilament structure

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 -/- ) mou...

Full description

Saved in:
Bibliographic Details
Published inCommunications biology Vol. 7; no. 1; p. 648
Main Authors Hessel, Anthony L., Kuehn, Michel N., Han, Seong-Won, Ma, Weikang, Irving, Thomas C., Momb, Brent A., Song, Taejeong, Sadayappan, Sakthivel, Linke, Wolfgang A., Palmer, Bradley M.
Format Journal Article
LanguageEnglish
Published London Nature Publishing Group UK 27.05.2024
Nature Publishing Group
Springer Nature
Nature Portfolio
Subjects
Online AccessGet full text

Cover

Loading…
More Information
Summary: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. A study on mice without fast-isoform Myosin Binding Protein C (MyBP-C) suggests that this isoform is a critical determinant of contraction performance via control of sarcomeric motor proteins.
Bibliography:ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
content type line 23
AC02-06CH11357
USDOE
ISSN:2399-3642
2399-3642
DOI:10.1038/s42003-024-06265-8