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 PK, Winkler H, Taylor K, Zoghbi ME, Craig RW, Padron R, Squire JM, Liu J. (2011). Direct visualization of myosin-binding protein C bridging myosin and actin filaments in intact muscle. Craig Lab Publications. https://doi.org/10.1073/pnas.1103216108. Retrieved from https://escholarship.umassmed.edu/craig/22