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. 2007 Mar 16;367(1):36-41.
doi: 10.1016/j.jmb.2006.12.063. Epub 2006 Dec 28.

Radial displacement of myosin cross-bridges in mouse myocardium due to ablation of myosin binding protein-C

Brett A Colson  1 , Tanya Bekyarova, Daniel P Fitzsimons, Thomas C Irving, Richard L Moss
Affiliations

Radial displacement of myosin cross-bridges in mouse myocardium due to ablation of myosin binding protein-C

Brett A Colson et al. J Mol Biol. .

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, I(11)/I(10), 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 ( approximately 30%) in the I(11)/I(10) 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 ( approximately 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.

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Figures

Figure 1
Figure 1
Western blot displaying cMyBP-C band region (140 kD M.W.) present in wild-type and absent in cMyBP-C-/- skinned myocardium following x-ray experiment.
Figure 2
Figure 2
1,0 and 1,1 equatorial reflection intensity peak profiles and patterns from WT and KO skinned myocardium.
Figure 2
Figure 2
1,0 and 1,1 equatorial reflection intensity peak profiles and patterns from WT and KO skinned myocardium.
See this image and copyright information in PMC

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