SAXS STUDIES OF THE CNTF-ASSOCIATED QUATERNARY COMPLEX

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 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)的四元复合体与其？受体(CNTFR)、gp130和LIF受体(LIFR)在肥胖控制中的作用。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. 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.