SAXS STUDIES OF THE CNTF-ASSOCIATED QUATERNARY COMPLEX

CNTF 相关第四纪杂岩的 SAXS 研究

• 批准号: 8362171
• 负责人: K CHRISTOPHER R GARCIA
• 金额: $ 0.03万
• 依托单位: STANFORD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-03-01 至 2012-02-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8362171
• 关键词: Binding; Ciliary Neurotrophic Factor; Complex; Crystallography; Funding; Goals; Grant; Ligands; Membrane; Molecular Conformation; National Center for Research Resources; Obesity; Principal Investigator; Radiation; Research; Research Infrastructure; Resources; Signal Transduction; Source; Structure; United States National Institutes of Health; cost; extracellular; interest; leukemia inhibitory factor receptor; receptor; structural biology

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. 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.

该子项目是利用资源的众多研究子项目之一 由 NIH/NCRR 资助的中心拨款提供。子项目的主要支持 并且子项目的主要研究者可能是由其他来源提供的， 包括其他 NIH 来源。 子项目可能列出的总成本 代表子项目使用的中心基础设施的估计数量， NCRR 赠款不直接向子项目或子项目工作人员提供资金。 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，以便理解为什么信号效应子的结合会导致受体的构象变化，以及为什么这种变化需要跨膜信号转导。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（如果有的话）。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）来解析一个重要的多组分组装体的整体构象：睫状神经营养因子（CNTF）与其α受体（CNTFR）、gp130和LIF受体（LIFR）相关的四元复合物，这对肥胖的控制具有影响。由于其结晶态衍射质量较差，我们相信 SAXS 将成为揭示其整体结构的有力替代方案。