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

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 肌球蛋白结合蛋白-C(MyBP-C)是一种粗大的细丝辅助蛋白，在心肌中起着调节肌动蛋白跨桥相互作用的作用，但其内在机制尚不清楚。为了探讨cMyBP-C功能的结构基础，我们用同步加速器小角X射线衍射法测量了野生型(WT)和cMyBP-C空白型(cMyBP-C/)心肌组织的微丝间距和赤道强度比I11/I10。 在松弛心肌中，cMyBP-C消融可导致横桥向远离粗丝的径向移位，cMyBP-C/(0.37±0.03)心肌的I11/I10比值较Towt(0.28±0.01)显著增加(±lt；30%)。而cMyBP-C/心肌的晶格间距(44.18(？0.68)nm)比WT(42.95(？0.43)nm)大，但差异无统计学意义。此外，与WT相比，cMyBP-C/心肌中肌丝格子中的液样无序明显更大(&lt；40%)。这些结果与我们的工作假设是一致的，即cMyBP-C通常作用于将肌球蛋白跨桥连接到更靠近粗丝骨架的位置，从而降低跨桥与肌动蛋白结合的可能性，并限制细丝的协同激活。这项工作已被《分子生物学杂志》接受并于2007年发表