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

该副本是使用众多研究子项目之一 由NIH/NCRR资助的中心赠款提供的资源。子弹和 调查员（PI）可能已经从其他NIH来源获得了主要资金， 因此可以在其他清晰的条目中代表。列出的机构是 对于中心，这是调查员的机构。 肌球蛋白结合蛋白-C（CMYBP-C）是一种较厚的细丝辅助蛋白，在心肌功能中，可以调节跨桥与肌动蛋白相互作用的动力学；但是，尚不清楚基本机制。为了探索CMYBP-C功能的结构基础，我们使用同步子低角度X射线衍射来测量与野生型（WT）和CMYBP-C-CMYBP-CMYBP-C / CMYBP-C /）中脱皮的心肌制剂中的皮肤心肌制剂中的I11 / I10。 在放松的心肌中，CMYBP-C的消融似乎导致横桥径向脱离厚细丝，因为与WT相比，CMYBP-C /（0.37€0.03）的I11 / I10比率显着增加（<30％）。与WT（42.95（42.95（0.43）nm）相比，晶格间距在CMYBP-C /心肌（44.18（0.68）nm）中往往更大，但差异在统计上并不显着。此外，与WT相比，CMYBP-C /心肌的肌丝晶格中的液样疾病明显更大（<40％）。这些结果与我们的工作假设是一致的：CMYBP-C通常对肌球蛋白跨桥的关系更接近厚的细丝主链，从而降低了跨桥与肌动蛋白结合并限制薄丝的合作激活的可能性。这项工作已被接受于2007年在分子生物学杂志上发表。