X-RAY CRYSTALLOGRAPHY OF IMMUNE-RELATED MOLECULES

免疫相关分子的 X 射线晶体学

• 批准号: 8362147
• 负责人: IAN A WILSON
• 金额: $ 1.08万
• 依托单位: STANFORD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-03-01 至 2012-02-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8362147
• 关键词: Amyloidosis; Antibodies; CD1 Antigens; Complex; Drug Design; Enzymes; Evolution; Funding; Glycoproteins; Grant; HIV Envelope Protein gp120; HIV-1; Hemagglutinin; Human; Immune; Immune system; Immunologic Receptors; Influenza; Laboratories; Lampreys; Major Histocompatibility Complex; Malignant Neoplasms; National Center for Research Resources; Neuraminidase; Phosphoribosylglycinamide formyltransferase; Prealbumin; Principal Investigator; Proteins; Radiation; Research; Research Infrastructure; Resources; Shark; Source; Structure; T-Cell Receptor; Toll-like receptors; United States National Institutes of Health; Viral Antigens; Virus; Work; X-Ray Crystallography; base; cost; influenzavirus; inhibitor/antagonist; interest; neutralizing antibody; phosphoribosylaminoimidazolecarboxamide formyltransferase; programs; structural biology; synchrotron radiation

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. 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.

这个子项目是许多利用资源的研究子项目之一 由NIH/NCRR资助的中心拨款提供。子项目的主要支持 而子项目的主要调查员可能是由其他来源提供的， 包括其它NIH来源。 列出的子项目总成本可能 代表子项目使用的中心基础设施的估计数量， 而不是由NCRR赠款提供给子项目或子项目工作人员的直接资金。 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、CD 1分子和Toll样受体，以及它们的细胞辅因子。我们有一个广泛的项目，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gp 120和gp 41（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感兴趣，并正在研究鲨鱼和七鳃鳗的免疫受体，以了解它们与哺乳动物的免疫受体相比如何。我们正在研究的许多蛋白质都是糖蛋白，它们的构象很弱，因此使用同步辐射对它们的结构测定至关重要。除了免疫系统相关的工作，我们正在研究酶GAR transformylase和AICAR transformylase，与抑制剂的复合物，在抗癌结构为基础的药物设计的程序，也与抗淀粉样变性抑制剂的复合物人甲状腺素运载蛋白。