X-RAY STUDIES OF SOLUBLE IL-10R2: AIDS ASSOCIATED LYMPHOMA

这个子项目是利用由NIH/NCRR资助的中心拨款提供的资源的许多研究子项目之一。子项目和调查员(PI)可能从另一个NIH来源获得了主要资金，因此可能会出现在其他CRISE条目中。列出的机构是针对中心的，而不一定是针对调查员的机构。IL-10是一种α-螺旋细胞因子，通过抑制促炎细胞因子的合成以及阻止巨噬细胞作为抗原提呈细胞而显示出强大的抗炎特性。因此，目前正在研究IL-10作为炎症性肠病或器官移植排斥反应的治疗方法。IL-10还可以刺激活化的B细胞的生长和分化，并被认为是一种自分泌生长因子，与多种B细胞恶性肿瘤有关，包括急性淋巴细胞白血病、慢性淋巴细胞白血病、Burkitt淋巴瘤和艾滋病相关淋巴瘤。利用SSRL束线9-2，我们测定了人IL-10与其高亲和力受体(Kd~1 nm)IL-10R1结合的MAD结构。然而，IL-10需要第二个低亲和力(Kd~1 mM)受体IL-10R2来启动其生物学活性。对IL-10R2的结构研究将为IL-10信号如何启动提供重要的新信息。

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.