Structural Biology Core

结构生物学核心的目标有三个：(1)确定HIV包膜糖蛋白各种构象的结构(特别是在成熟病毒粒子表面发现的未连接状态下)，以便尽可能完整地了解其构象转变的“分子电影”；(2)与CHAVI项目的研究人员进行合作结构测定(特别是回答有关分子背景如何影响gp120可变环的免疫原性的问题)或在适当时帮助组织与其他实验室的这种合作；(3)交流复合体 向艾滋病毒社区的其他人，特别是这个CHAVI联盟的其他研究人员提供包膜构象变化的图片。具体目的包括：(1)根据最近确定的未连接SIV gp120的结构，通过引入二硫键来产生稳定形式的未连接的HIV-1 gp120用于结构研究；(2)利用第一个目的的结果产生稳定的gp140三聚体用于结构研究；(3)利用前两个目的的结果分析HIV包膜蛋白在其未连接构象中的免疫原性。根据CHAVI联盟的其他实验结果，将确定来自“广泛的”中和单抗的某些Fab片段的结构，这些片段与多肽抗原或与gp120或gp140具有适当的 表位。通过开发一种交互式分子动画，当新的结构数据出现时，将会有一个持续的努力来传达包膜构象变化的复杂性。

The goals of the structural biology core are threefold: (1) to determine structures of the HIV envelope glycoprotein in its various conformations (and especially in the unliganded state found on the surface of a mature virion), in order to have as complete a "molecular movie" of its conformational transitions as possible; (2) to engage in collaborative structure determinations with investigators in the CHAVI project (in particular to answer questions about how molecular context influences immunogenicity of gp120 variable loops) or to help organize such collaborations with other laboratories when appropriate; (3) to communicate the complex picture of envelope conformational transformations to the rest of the HIV community and in particular to the other investigators in this CHAVI consortium. Specific aims include: (1) generating stabilized forms of unliganded HIV-1 gp120 for structural studies, by introducing disulfide bonds based on the recently determined structure of unliganded SIV gp120; (2) using the results of the first aim to produce stabilized gp140 trimers for structural studies; (3) using the results of the first two aims to analyze the immunogenic properties of the HIV envelope protein in its unliganded conformation. Depending on the outcome of other experiments in the CHAVI consortium, structures will be determined for certain Fab fragments from "broadly" neutralizing mAbs, in complex with peptide antigens or with gp120 or gp140 bearing the appropriate epitopes. There will be an ongoing effort to communicate the complexities of envelope conformational changes, through development of an interactive molecular animation that incorporates new structural data as they emerge.