HIV GLYCOPROTEIN STRUCTURE

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 HIV-1包膜糖蛋白(gp120/gp41)在病毒感染和致病过程中起重要作用。在被认为具有广谱中和活性的六株单抗中，有三株(2F5、4E10、Z13e1)与gp41的膜近端外区(MPER)结合。这使得MPER成为开发免疫原的理想模板，可以诱导具有与这些mAbb相似特性的抗体，长期目标是开发可用作新型艾滋病毒疫苗的抗原。为了给合理的抗原设计提供结构基础，我们构建了MPER结构，HR1-54Q，用于X射线结晶学研究，以提供高分辨率的原子坐标。该结构很可能代表gp41融合后的形式，我们希望该结构将为适合HIV疫苗开发的gp41抗原设计提供合理的基础。

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. HIV-1 envelope glycoprotein (gp120/gp41) plays a critical role in virus infection and pathogenesis. Three of the six monoclonal antibodies (mAbs) considered to have broadly neutralizing activities (2F5, 4E10, Z13e1) bind to the membrane proximal external region (MPER) of gp41. This makes the MPER a desirable template for developing immunogens that can elicit antibodies with properties similar to these mAbs, with a long-term goal of developing antigens that could serve as novel HIV vaccines. In order to provide a structural basis for rational antigen design, an MPER construct, HR1-54Q, was generated for x-ray crystallographic study to provide high-resolution atomic coordinates. The structure will most likely represents a post-fusion form of gp41 and we hope that the structure will provide a rational basis for gp41 antigen design suitable for HIV vaccine development.