Department of Cell Biology
Actins; Animals; Biophysical Phenomena; Carrier Proteins; Electron Microscope Tomography; Freeze Substitution; Humans; Imaging, Three-Dimensional; Models, Molecular; Muscle, Skeletal; Myosins; Ranidae
Myosin-binding protein C (MyBP-C) is a thick filament protein playing an essential role in muscle contraction, and MyBP-C mutations cause heart and skeletal muscle disease in millions worldwide. Despite its discovery 40 y ago, the mechanism of MyBP-C function remains unknown. In vitro studies suggest that MyBP-C could regulate contraction in a unique way--by bridging thick and thin filaments--but there has been no evidence for this in vivo. Here we use electron tomography of exceptionally well preserved muscle to demonstrate that MyBP-C does indeed bind to actin in intact muscle. This binding implies a physical mechanism for communicating the relative sliding between thick and thin filaments that does not involve myosin and which could modulate the contractile process.
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DOI of Published Version
Proc Natl Acad Sci U S A. 2011 Jul 12;108(28):11423-8. Epub 2011 Jun 24. Link to article on publisher's site
Proceedings of the National Academy of Sciences of the United States of America
Luther, Pradeep K.; Winkler, Hanspeter; Taylor, Kenneth; Zoghbi, Maria E.; Craig, Roger W.; Padron, Raul; Squire, John M.; and Liu, Jun, "Direct visualization of myosin-binding protein C bridging myosin and actin filaments in intact muscle" (2011). Craig Lab Publications. 22.