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This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. 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) myocardiumas compared toWT(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. This work has been accepted for publication in Journal of Molecular Biology in 2007
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Rodent Holding for WIMR Cardiovascular Research
  • 批准号:
    8524546
  • 项目类别:
  • 资助金额:
    $44.58万
  • 财政年份:
    2013
  • 负责人:
    Richard L Moss
  • 依托单位:
Arrhythmias in HCM Due to Mutation in cMyBP-C
  • 批准号:
    8134106
  • 项目类别:
  • 资助金额:
    $62.68万
  • 财政年份:
    2010
  • 负责人:
    Richard L Moss
  • 依托单位:
ROLE OF MY-BP-C MODULATION OF CARDIAC CONTRACTION
  • 批准号:
    8168615
  • 项目类别:
  • 资助金额:
    $6.29万
  • 财政年份:
    2010
  • 负责人:
    Richard L Moss
  • 依托单位:
Calcium Triggered Arrhythmias and Sudden Cardiac Arrest
  • 批准号:
    7906640
  • 项目类别:
  • 资助金额:
    $194.25万
  • 财政年份:
    2009
  • 负责人:
    Richard L Moss
  • 依托单位:
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