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

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68 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

Bibliographical note

Funding Information:
We thank Heather King and Krystyna Shioura for technical assistance with X-ray data analysis. This work was supported by funding from the National Institutes of Health (R3782900) (to R. L. M.). Use of the Advanced Photon Source was supported by the US Department of Energy, Basic Energy Sciences, and Office of Science, under contract no. W-31-109-ENG-38. BioCAT is a National Institutes of Health-supported Research Center (RR-08630).

Keywords

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

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