NEF_TCRZ_PROJECT

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目及 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者的研究机构。 人类免疫缺陷病毒（HIV-1，HIV-2）和猿猴免疫缺陷病毒（SIV）阴性因子（Nef）是在病毒复制周期早期大量表达的27-34 kDa病毒辅助蛋白。Nef在病毒复制过程中可分散，在增加HIV感染的致病性和毒力方面发挥重要作用，部分是通过调节T细胞活性，推测是通过其与T细胞受体（TCR ζ）的ζ信号传导链的相互作用。目前，我们已经结晶了一个包含SIV Nef的核心结构域和TCR ζ片段的复合物，并在我们的国内来源获得了高达6-8A的衍射数据。使用更强大的光束线将产生更高分辨率的数据，这将允许确定复合体的高分辨率结构。Nef-TCR ζ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，而且还将提供对Nef如何通过TCR诱导免疫调节活性的深入了解。

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.