NEF_TCRZ_PROJECT

NEF_TCRZ_项目

• 批准号: 7957263
• 负责人: Lawrence J. Stern
• 金额: $ 1.11万
• 依托单位: BROOKHAVEN SCIENCE ASSOC-BROOKHAVEN LAB
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-07-01 至 2010-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7957263
• 关键词: Complex; Computer Retrieval of Information on Scientific Projects Database; Crystallography; Data; Funding; Grant; HIV; HIV Infections; HIV-1; HIV-2; Home environment; Institution; Light; Pathogenicity; Play; Proteins; Research; Research Personnel; Resolution; Resources; Role; SIV; Signal Transduction; Site; Source; Structure; Synchrotrons; T-Cell Receptor; T-Lymphocyte; United States National Institutes of Health; Viral; Virulence; beamline; insight

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. Human immunodeficiency virus (HIV-1, HIV-2) and simian immunodeficiency virus (SIV) negative factor (Nef) is a 27-34 kDa viral accessory protein expressed in abundance early in the viral replicative cycle. Dispensable during viral replication, Nef plays an important role in increasing the pathogenicity and virulence of an HIV infection in part by modulation of T-cell activity, presumably through its demonstrated interaction with the zeta signaling chain of the T-cell receptor (TCRzeta). At present, we have crystallized a complex containing the core domain of SIV Nef and a fragment of the TCRzeta and obtained diffraction data up to 6-8A at our home source. Access to a more powerful beamline will result in higher resolution data that should allow for determination of a high resolution structure of the complex. Structural details of the Nef-TCRzeta complex will reveal not only the interaction sites on each protein but also provide insight into how Nef induces immunomodulatory activity through the TCR.

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。 人类免疫缺陷病毒（HIV-1、HIV-2）和猿猴免疫缺陷病毒（SIV）负因子（Nef）是一种 27-34 kDa 的病毒辅助蛋白，在病毒复制周期早期大量表达。 Nef 在病毒复制过程中是可有可无的，在增加 HIV 感染的致病性和毒力方面发挥着重要作用，部分是通过调节 T 细胞活性，推测是通过其与 T 细胞受体 (TCRzeta) 的 zeta 信号链的相互作用来实现。目前，我们已经结晶出包含SIV Nef核心结构域和TCRzeta片段的复合物，并在我们的来源获得了高达6-8A的衍射数据。获得更强大的光束线将产生更高分辨率的数据，从而可以确定复合物的高分辨率结构。 Nef-TCRzeta 复合物的结构细节不仅将揭示每种蛋白质上的相互作用位点，还将深入了解 Nef 如何通过 TCR 诱导免疫调节活性。