ROLE OF CMYBP-C IN THE REGULATION OF MYOCARDIUM

CMYBP-C 在心肌调节中的作用

• 批准号: 7601777
• 负责人: Richard L Moss
• 金额: $ 2.36万
• 依托单位: ILLINOIS INSTITUTE OF TECHNOLOGY
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-04-01 至 2008-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7601777
• 关键词: Ablation; Actins; Binding; Computer Retrieval of Information on Scientific Projects Database; Disease; Funding; Grant; Institution; Journals; Kinetics; Liquid substance; Measures; Microfilaments; Molecular Biology; Muscle function; Myocardial; Myocardium; Myosin ATPase; Preparation; Proteins; Publications; Radial; Regulation; Research; Research Personnel; Resources; Role; Skin; Source; Statistically Significant; Synchrotrons; Thick Filament; Thin Filament; United States National Institutes of Health; Vertebral column; Work; X ray diffraction analysis; X-Ray Diffraction; base; myosin-binding protein C

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

该子项目是利用该技术的众多研究子项目之一 资源由 NIH/NCRR 资助的中心拨款提供。 研究者 (PI) 可能已从 NIH 的另一个来源获得主要资金， 因此可以出现在其他 CRISP 条目中 列出的机构是。 对于中心来说，它不一定是研究者的机构。 肌球蛋白结合蛋白-C (cMyBP-C) 是一种粗丝辅助蛋白，在心肌中发挥调节与肌动蛋白跨桥相互作用的动力学的作用；然而，其潜在机制尚不清楚。 cMyBP-C 函数，我们使用同步加速器低角度 X 射线衍射来测量带皮心肌中的丝间晶格间距和赤道强度比 I11/I10从野生型 (WT) 和 cMyBP-C null (cMyBP-C / ) 中分离出制剂。 在松弛的心肌中，cMyBP-C 的消融似乎导致横桥远离粗肌丝的径向位移，因为 cMyBP-C 的 I11/I10 比率显着增加 (<30%) / ( 0.37¿ 0.03) 心肌与WT(0.28¿0.01)相比，而晶格间距往往更大。 cMyBP-C / 心肌 (44.18(¿0.68) nm) 与 WT (42.95(¿0.43) nm) 相比，差异无统计学意义。此外，肌丝晶格中的液体状紊乱明显更大 (< 40%)。与 WT 相比，cMyBP-C / 心肌中的（更大）这些结果与我们的工作假设一致，即 cMyBP-C 通常起到束缚作用。肌球蛋白的跨桥更靠近粗肌丝主链，从而降低了跨桥与肌动蛋白结合的可能性，并限制了细肌丝的协同激活。这项工作已于 2007 年在《分子生物学杂志》上发表。