X-RAY CRYSTALLOGRAPHY OF IMMUNE-RELATED MOLECULES

这个子项目是利用资源的许多研究子项目之一。 由NIH/NCRR资助的中心拨款提供。对子项目的主要支持 子项目的首席调查员可能是由其他来源提供的， 包括美国国立卫生研究院的其他来源。为子项目列出的总成本可能 表示该子项目使用的中心基础设施的估计数量， 不是由NCRR赠款提供给次级项目或次级项目工作人员的直接资金。 我们的实验室对与我们的适应性免疫系统和先天免疫系统有关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体分子、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它们的病毒抗原gp120和gp41(来自HIV-1)以及血凝素和神经氨酸酶(来自流感)的复合体。此外，我们对免疫系统的进化很感兴趣，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同行的比较。我们正在研究的许多蛋白质都是糖蛋白，它们倾向于弱衍射，所以使用同步辐射对它们的结构测定是至关重要的。除了与免疫系统相关的工作外，我们还在研究GAR转移酶和AICAR转移酶与抑制剂的复合体，在基于结构的抗癌药物设计中，以及人转甲状腺素与抗淀粉样变抑制剂的复合体中。

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.