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。对子项目的主要支持 子项目的首席调查员可能是由其他来源提供的， 包括美国国立卫生研究院的其他来源。为子项目列出的总成本可能 表示该子项目使用的中心基础设施的估计数量， 不是由NCRR赠款提供给次级项目或次级项目工作人员的直接资金。 我们有兴趣阐明细胞外受体及其同源配体复合体的结构细节和空间排列，以了解为什么信号效应器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。我们部分地通过X射线结晶学实现了这一目标。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，我们计划采取一种不同的方法，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的全球构象：睫状神经营养因子(CNTF)及其α受体(CNTFR)、gp130和LIF受体(LIFR)的四元复合体，这对控制肥胖具有重要意义。由于其在结晶状态下的衍射质量较差，我们相信SAXS将是揭示其全局结构的有力替代方案。

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.