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

被引:66
作者
Colson, Brett A. [1 ]
Bekyarova, Tanya
Fitzsimons, Daniel P.
Irving, Thomas C.
Moss, Richard L.
机构
[1] Univ Wisconsin, Sch Med, Dept Physiol, Madison, WI 53711 USA
[2] IIT, CSRRI, Chicago, IL 60607 USA
[3] IIT, Dept BCPS, Chicago, IL 60607 USA
关键词
cMyBP-C; myocardium; structure; X-ray; myosin;
D O I
10.1016/j.jmb.2006.12.063
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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 (similar to 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 incMyBP-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 (similar to 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. Published by Elsevier Ltd.
引用
收藏
页码:36 / 41
页数:6
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