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

可溶性 IL-10R2 的 X 射线研究：艾滋病相关淋巴瘤

• 批准号: 7370363
• 负责人: MARK R WALTER
• 金额: $ 0.05万
• 依托单位: STANFORD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-03-01 至 2007-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7370363
• 关键词: RAY; STUDIES; SOLUBLE; IL; 10R2

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.

该子项目是利用NIH/NCRR资助的中心赠款提供的资源的许多研究子项目之一。子项目和研究者（PI）可能从另一个NIH来源获得主要资金，因此可以在其他CRISP条目中表示。所列机构为中心，不一定是研究者所在机构。IL-10是一种α-螺旋细胞因子，其通过抑制促炎细胞因子的合成以及防止巨噬细胞充当抗原呈递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的治疗。IL-10还刺激活化的B细胞的生长和分化，并且在几种B细胞恶性肿瘤（包括急性淋巴细胞白血病、慢性淋巴细胞白血病、伯基特淋巴瘤和AIDS相关淋巴瘤）中作为自分泌生长因子而被牵涉。使用SSRL Beam Line 9-2，我们已经确定了与其高亲和力受体（Kd~ 1 nM）IL-10 R1结合的人IL-10的MAD结构。然而，IL-10需要第二个低亲和力（Kd~ 1 mM）受体IL-10 R2来启动其生物学活性。对IL-10 R2的结构研究将为IL-10信号传导如何启动提供重要的新信息。