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...
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Published in | Communications biology Vol. 7; no. 1; p. 648 |
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Main Authors | , , , , , , , , , |
Format | Journal Article |
Language | English |
Published |
London
Nature Publishing Group UK
27.05.2024
Nature Publishing Group Springer Nature Nature Portfolio |
Subjects | |
Online Access | Get full text |
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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. |
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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 |