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. IL-10 is an alpha-helical cytokine that displays powerful anti-inflammatory properties by inhibiting the synthesis of pro-inflammatory cytokines as well as preventing macrophages from serving as antigen presenting cells. As a result, IL-10 is currently being studied as a treatment of inflammatory bowel disease or organ transplant rejection. IL-10 also stimulates the growth and differentiation of activated B cells and has been implicated as an autocrine growth factor in several B cell malignancies including acute lymphoblastic leukemia, chronic lymphocytic leukemia, Burkitt's lymphoma, and AIDS-associated lymphoma. Using SSRL Beam Line 9-2, we have determined MAD structure of human IL-10 bound to its high affinity receptor (Kd~1nM), IL-10R1. However, IL-10 requires a second low affinity (Kd~1mM) receptor, IL-10R2, to initiate its biological activities. Structural studies on IL-10R2 will provide important new information on how IL-10 signaling is initiated.
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