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. : Members of the interleukin 1 (IL 1) family of cytokines play major roles in host defense and immune system regulation in infectious and inflammatory diseases. They activate the biological response in effector cells by binding to the extra cellular domain of two IL 1 receptor family members, the primary receptor and the co receptor, forming a heterotrimeric signaling holocomplex. Despite the importance and the long interest in IL 1 cytokine/receptor complexes, only the IL 1b/IL 1 receptor I (IL 1 RI) and IL 1Ra/IL 1 RI complexes have been characterized on a structural level to date;information on the molecular arrangement of the heterotrimeric complexes is not available. Il-33 is a recently discovered IL-1 like cytokine, which was shown to be involved in T-helper-cell type 2 mediated immune responses, such as asthma or allergy. We used small angle x-ray scattering in combination with NMR chemical shift perturbation data and detailed biochemical characterization to obtain a consistent model of the IL-33/ST2 complex in solution. The model shows that IL 33 forms a complex with ST2 that is similar to the IL 1b/IL 1 RI complex. We extended our SAXS analysis to the IL 33/ST2/IL 1RacP and IL 1b/IL 1 RI/IL 1RacP complexes and propose a general model of the molecular arrangement of the IL 1 trimeric signaling complexes.
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