SAXS STUDIES OF THE CNTF-ASSOCIATED QUATERNARY COMPLEX

CNTF 相关第四纪杂岩的 SAXS 研究

• 批准号: 7954452
• 负责人: K CHRISTOPHER R GARCIA
• 金额: $ 0.02万
• 依托单位: STANFORD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-03-01 至 2010-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7954452
• 关键词: Binding; Ciliary Neurotrophic Factor; Complex; Computer Retrieval of Information on Scientific Projects Database; Crystallography; Funding; Goals; Grant; Institution; Ligands; Membrane; Molecular Conformation; Obesity; Research; Research Personnel; Resources; Signal Transduction; Source; Structure; United States National Institutes of Health; extracellular; interest; leukemia inhibitory factor receptor; receptor; structural biology; synchrotron radiation

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. We are interested in elucidating the structural details and spatial arrangements of extracellular receptors in complex with their cognate ligands in order to understand why the binding of signaling effectors results in conformational changes of the receptors, and why such changes warrant signal transduction across the membrane. We achieve this goal in part via x-ray crystallography. However, this is vastly depending on the diffracting quality of the crystals, if at all obtainable. Currently we plan to take a different approach, by using small-angle x-ray scattering (SAXS) to resolve the global conformation of an important multi-component assembly: the quaternary complex of ciliary neurotrophic factor (CNTF) in association with its alpha receptor (CNTFR), gp130 and LIF receptor (LIFR), which has implications on the control of obesity. Due to its poor diffraction quality in crystalline state, we believe SAXS will be a powerful alternative to reveal its global structure.

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。 我们有兴趣阐明细胞外受体与其同源配体复合物的结构细节和空间排列，以了解为什么信号效应物的结合会导致受体的构象变化，以及为什么这种变化保证信号跨膜传导。我们通过X射线晶体学部分实现了这一目标。然而，这在很大程度上取决于晶体的衍射质量，如果可以获得的话。目前，我们计划采取不同的方法，通过使用小角X射线散射（SAXS）来解决一个重要的多组分组装的全局构象：睫状神经营养因子（CNTF）与其α受体（CNTFR），gp 130和LIF受体（LIFR）的四元复合物，这对控制肥胖有影响。由于其在结晶状态下的衍射质量差，我们相信SAXS将是一个强大的替代来揭示其整体结构。