Radial Displacement of Myosin Cross-bridges in Mouse Myocardium due to Ablation of Myosin Binding Protein-C

Brett A. Colson, Tanya Bekyarova, Daniel P. Fitzsimons, Thomas C. Irving, Richard L. Moss

Research output: Contribution to journalArticle

60 Scopus citations

Abstract

Myosin binding protein-C (cMyBP-C) is a thick filament accessory protein, which in cardiac muscle functions to regulate the kinetics of cross-bridge interaction with actin; however, the underlying mechanism is not yet understood. To explore the structural basis for cMyBP-C function, we used synchrotron low-angle X-ray diffraction to measure interfilament lattice spacing and the equatorial intensity ratio, I11/I10, in skinned myocardial preparations isolated from wild-type (WT) and cMyBP-C null (cMyBP-C-/-). In relaxed myocardium, ablation of cMyBP-C appeared to result in radial displacement of cross-bridges away from the thick filaments, as there was a significant increase (∼30%) in the I11/I10 ratio for cMyBP-C-/- (0.37 ± 0.03) myocardium as compared to WT (0.28 ± 0.01). While lattice spacing tended to be greater in cMyBP-C-/- myocardium (44.18 ± 0.68 nm) when compared to WT (42.95 ± 0.43 nm), the difference was not statistically significant. Furthermore, liquid-like disorder in the myofilament lattice was significantly greater (∼40% greater) in cMyBP-C-/- myocardium as compared to WT. These results are consistent with our working hypothesis that cMyBP-C normally acts to tether myosin cross-bridges nearer to the thick filament backbone, thereby reducing the likelihood of cross-bridge binding to actin and limiting cooperative activation of the thin filament.

Original languageEnglish (US)
Pages (from-to)36-41
Number of pages6
JournalJournal of Molecular Biology
Volume367
Issue number1
DOIs
StatePublished - Mar 16 2007
Externally publishedYes

Keywords

  • X-ray
  • cMyBP-C
  • myocardium
  • myosin
  • structure

ASJC Scopus subject areas

  • Structural Biology
  • Molecular Biology

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