Structural Biology Core

结构生物学核心

• 批准号: 8294664
• 负责人: STEPHEN COPLAN HARRISON
• 金额: $ 103.6万
• 依托单位: DUKE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-07-01 至 2013-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8294664
• 关键词: AIDS/HIV problem; Antigens; Collaborations; Communities; Complex; Data; Development; Epitopes; Fab Immunoglobulins; Glycoproteins; Goals; HIV; HIV Envelope Protein gp120; HIV envelope protein; HIV-1; Immunology; Laboratories; Molecular; Molecular Conformation; Outcome; Peptides; Property; Research Personnel; Rest; Structure; Surface; Vaccines; Virion; animation; base; conformational conversion; disulfide bond; immunogenic; immunogenicity; movie; neutralizing monoclonal antibodies; research study; simian immunodeficiency virus gp120; structural biology

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.

结构生物学核心的目标有三个：(1)确定HIV包膜糖蛋白在其各种构象中的结构（特别是在成熟病毒粒子表面发现的无配体状态），以便尽可能完整地了解其构象转变的“分子电影”；(2)与CHAVI项目中的研究人员合作确定结构（特别是回答有关分子环境如何影响gp120可变环的免疫原性的问题）或在适当的时候帮助组织与其他实验室的此类合作；(3)沟通复杂