SAXS STUDIES OF THE CNTF-ASSOCIATED QUATERNARY COMPLEX

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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.