STRUCTURAL STUDIES ON CYTOKINE-RECEPTOR COMPLEXES

Stanford University, Stanford CA

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Abstract

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. The overall goal of our work is to define the structural basis of class-2 cytokine signaling. In this proposal, we seek define the structure of the receptor assembly that mediates IL-20 signaling. IL-20 forms a ternary complex with IL-20R1 and IL-20R2, which are cell surface receptors that signal through STAT3. At this time, no ternary receptor complexes have been reported for any class 2 cytokine. The biology of IL-20 suggests it mediates cross-talk between the immune and epithelial cells. Recent data suggests IL-20 is critical in the pathogenesis of Psoriasis and may be target to control the disease. Successful completion of the IL-20/IL-20R1/IL-20R2 complex will serve as the prototype 3-dimensional structure of a class 2 cytokine ternary complex and may be used to design novel therapies for Psoriasis. Crystals of the complex have been grown. Synchrotron radiation is needed to screen crystals, obtain the highest possible resolution data, and phase the structure using SAD/MAD phasing methods.