SAXS STUDIES OF THE CNTF-ASSOCIATED QUATERNARY COMPLEX

这个子项目是利用资源的许多研究子项目之一 由NIH/NCRR资助的中心拨款提供。次级项目的主要支助 而子项目的主要调查员可能是由其他来源提供的， 包括其它NIH来源。 列出的子项目总成本可能 表示子项目使用的中心基础设施的估计数量， 而不是由NCRR赠款提供给子项目或子项目工作人员的直接资金。 我们感兴趣的是阐明与其同源配体复合的细胞外受体的结构细节和空间排列，以了解为什么信号效应物的结合导致受体的构象变化，以及为什么这种变化保证跨膜信号转导。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。

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.