SAXS STUDIES OF THE CNTF-ASSOCIATED QUATERNARY COMPLEX

这个子项目是许多利用 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）来解决全球构象的一个重要的多组分组装：四元复合物的睫状神经营养因子（CNTF）与其？受体（CNTFR）、gp 130和LIF受体（LIFR），这对肥胖的控制具有意义。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. 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 ? 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.