PROTEIN DYNAMICS FROM NMR WITH RHOMBIC LOCAL POTENTIALS

具有菱形局部势的 NMR 蛋白质动力学

• 批准号: 7420503
• 负责人: EVA MEIROVITCH
• 金额: $ 1.58万
• 依托单位: CORNELL UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-09-15 至 2007-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7420503
• 关键词: adenylate kinase; calmodulin; carbon; diffusion; model; peptides; proteins; relaxation; spine

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. 5N-1H spin relaxation is a powerful method for elucidating protein backbone dynamics. In order to derive as much information as possible from the experimental data a theoretical approach is needed which matches the integrity of currently available data. We have shown that the slowly relaxing local structure (SRLS) approach is capable of accomplishing this. Dominant phenomena such as dynamical coupling between the local motion of the probe (e.g., N-H bond) and the global tumbling of the protein, and general features of local geometry, are explicitly included in SRLS. In recent work we have focused on the geometric aspects, in particular the symmetry of the mode-coupling potential, which reflects the local geometry about the 15N site. The symmetry of the potential depends on the symmetry of the local diffusion/local ordering frame, M, and the symmetry of the local director frame, C, which are illustrated below top. We found that the particular rhombic symmetry of the M frame is of the "nearly planar Ym-Ym" type, in agreement with the stereo-chemistry of the peptide plane and the N-H site. (crankshaft fluctuations and peptide-plane reorientation of adjacent carbon bonds in peptide backbone axis) are functionally important internal motions, which necessarily involve rhombic spatial restrictions, can be treated satisfactorily with SRLS whereas the model free approach is not able to explicitly allow for them. We found that a proper SRLS theory is required to discern such functionally important motions. We demonstrated this with examples of NMR relaxation data from adenylate kinase, calmodulin, binase and ribonuclease H. With mode-coupling and the local geometry properly accounted for, SRLS appears to match the quality of current 15N relaxation data in proteins. Thus SRLS provides insightful information on backbone dynamics which can be related directly to function.

该子项目是利用NIH/NCRR资助的中心赠款提供的资源的许多研究子项目之一。子项目和研究者（PI）可能从另一个NIH来源获得主要资金，因此可以在其他CRISP条目中表示。所列机构为中心，不一定是研究者所在机构。5 N-1H自旋弛豫是研究蛋白质骨架动力学的有效方法。为了从实验数据中获得尽可能多的信息，需要一种与当前可用数据的完整性相匹配的理论方法。我们已经表明，缓慢松弛的局部结构（SRLS）的方法是能够实现这一点。诸如探针的局部运动（例如，N-H键）和蛋白质的整体翻滚，以及局部几何的一般特征，明确地包括在SRLS中。在最近的工作中，我们一直专注于几何方面，特别是对称性的模式耦合潜力，这反映了当地的几何约15 N网站。势的对称性取决于局部扩散/局部有序框架M的对称性和局部指向矢框架C的对称性，它们在顶部下方示出。我们发现，特别是菱形对称的M框架是“近平面Ym-Ym”型，在协议的肽平面和N-H位点的立体化学。（曲轴波动和肽骨架轴中相邻碳键的肽平面重新取向）是功能上重要的内部运动，其必然涉及菱形空间限制，可以用SRLS令人满意地处理，而无模型方法不能明确地允许它们。我们发现，需要一个适当的SRLS理论来辨别这种功能上重要的运动。我们用腺苷酸激酶、钙调蛋白、双酶和核糖核酸酶H的核磁共振弛豫数据的例子证明了这一点。与模式耦合和当地的几何形状适当占，SRLS出现匹配的质量，目前的15 N弛豫数据在蛋白质。因此，SRLS提供了有见地的信息骨干动力学，可以直接相关的功能。