Direct visualization of myosin-binding protein C bridging myosin and actin filaments in intact muscle

Proc Natl Acad Sci U S A. 2011 Jul 12;108(28):11423-8. doi: 10.1073/pnas.1103216108. Epub 2011 Jun 24.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actins / chemistry
  • Actins / metabolism*
  • Actins / ultrastructure
  • Animals
  • Biophysical Phenomena
  • Carrier Proteins / chemistry
  • Carrier Proteins / metabolism*
  • Carrier Proteins / ultrastructure
  • Electron Microscope Tomography
  • Freeze Substitution
  • Humans
  • Imaging, Three-Dimensional
  • Models, Molecular
  • Muscle, Skeletal / chemistry
  • Muscle, Skeletal / metabolism*
  • Muscle, Skeletal / ultrastructure
  • Myosins / chemistry
  • Myosins / metabolism*
  • Myosins / ultrastructure
  • Ranidae


  • Actins
  • Carrier Proteins
  • myosin-binding protein C
  • Myosins