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的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 肌球蛋白结合蛋白-C（Myosin binding protein-C，cMyBP-C）是一种粗肌丝辅助蛋白，在心肌中起着调节与肌动蛋白跨桥相互作用的作用，但其作用机制尚不清楚。为了探索cMyBP-C功能的结构基础，我们使用同步辐射低角X射线衍射测量从野生型（WT）和cMyBP-C无效（cMyBP-C）分离的皮肤心肌制备物中的丝间晶格间距和赤道强度比I11/I10/). 在松弛心肌中，cMyBP-C的消融似乎导致横桥远离粗丝的径向位移，因为cMyBP-C的I11/I10比值显著增加（<30%）/ (0.37心肌瘤组（0.28 ± 0.01）例，对照组（0.03 ± 0.01）例。而cMyBP-C中的晶格间距倾向于更大，/ 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，在cMyBP-C中，肌丝晶格中的液体样紊乱明显更大（大于40%）。/ 与WT相比，这些结果与我们的工作假设一致，即cMyBP-C通常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。这项工作已被接受发表在2007年的分子生物学杂志