X-RAY CRYSTALLOGRAPHY OF IMMUNE-RELATED MOLECULES

免疫相关分子的 X 射线晶体学

• 批准号: 7722107
• 负责人: IAN A WILSON
• 金额: $ 0.12万
• 依托单位: STANFORD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-03-01 至 2009-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7722107
• 关键词: Amyloidosis; Antibodies; CD1 Antigens; Complex; Computer Retrieval of Information on Scientific Projects Database; Crystallography; Drug Design; Enzymes; Evolution; Funding; Glycoproteins; Grant; HIV Envelope Protein gp120; HIV Envelope Protein gp41; HIV-1; Hemagglutinin; Human; Immune; Immune system; Immunologic Receptors; Influenza; Institution; Laboratories; Lampreys; Malignant Neoplasms; Neuraminidase; Phosphoribosylglycinamide formyltransferase; Prealbumin; Proteins; Research; Research Personnel; Resources; Shark; Source; Structure; T-Cell Receptor; T-Lymphocyte; Toll-like receptors; United States National Institutes of Health; Viral Antigens; Virus; Work; base; influenzavirus; inhibitor/antagonist; interest; neutralizing antibody; phosphoribosylaminoimidazolecarboxamide formyltransferase; programs; synchrotron radiation

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. Our laboratory carries out structural studies of molecules involved in our adaptive and innate immune systems. These molecules include antibodies, T cell receptors, major histocompatibility complex molecules, CD1 molecules and Toll-like receptors, as well as their cellular co-factors. We have an extensive program studying neutralizing antibodies against the HIV-1 virus and the influenza virus, and will be studying complexes of these antibodies with their viral antigens gp120 and gp41 (from HIV-1) and hemagglutinin and neuraminidase (from influenza). In addition, we are interested in the evolution of the immune system and are studying immune receptors from shark and lamprey in order to see how they compare to their mammalian counterparts. Many of the proteins we are studying are glycoproteins that tend to diffract weakly, so the use of synchrotron radiation is critical for their structure determinations. In addition to the immune-system related work, we are studying the enzymes GAR transformylase and AICAR transformylase, in complex with inhibitors, in a program of anti-cancer structure-based drug design and also human transthyretin in complex with anti-amyloidosis inhibitors.

该子项目是利用该技术的众多研究子项目之一 资源由 NIH/NCRR 资助的中心拨款提供。子项目及 研究者 (PI) 可能已从 NIH 的另一个来源获得主要资金， 因此可以在其他 CRISP 条目中表示。列出的机构是 对于中心来说，它不一定是研究者的机构。 我们的实验室对参与我们的适应性和先天免疫系统的分子进行结构研究。这些分子包括抗体、T细胞受体、主要组织相容性复合物分子、CD1分子和Toll样受体，以及它们的细胞辅助因子。我们有一个广泛的计划，研究针对 HIV-1 病毒和流感病毒的中和抗体，并将研究这些抗体与其病毒抗原 gp120 和 gp41（来自 HIV-1）以及血凝素和神经氨酸酶（来自流感）的复合物。此外，我们对免疫系统的进化很感兴趣，并且正在研究鲨鱼和七鳃鳗的免疫受体，以便了解它们与哺乳动物对应物的比较。我们正在研究的许多蛋白质都是糖蛋白，其衍射能力较弱，因此同步加速器辐射的使用对于它们的结构测定至关重要。除了免疫系统相关工作外，我们还在基于抗癌结构的药物设计项目中研究与抑制剂复合的 GAR 转化酶和 AICAR 转化酶，以及与抗淀粉样变抑制剂复合的人转甲状腺素蛋白。