VIRAL MEMBRANE AND GLYCOPROTEIN STRUCTURE

病毒膜和糖蛋白结构

• 批准号: 2060009
• 负责人: DON C WILEY
• 金额: $ 17.98万
• 依托单位: HARVARD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1977
• 资助国家: 美国
• 起止时间: 1977-01-01 至 1995-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2060009
• 关键词: X ray crystallography; antibody inhibitor; antibody receptor; antigen receptors; arginine; carbopolycyclic compound; cardiac glycosides; chemical binding; disease /disorder model; genetic strain; glycoproteins; hemagglutinin; high performance liquid chromatography; ligands; membrane fusion; membrane model; membrane proteins; membrane structure; mutant; nuclear magnetic resonance spectroscopy; nucleic acid sequence; parainfluenza virus type 1; protein structure; receptor binding; recombinant DNA; sialate; site directed mutagenesis; surface antigens; thermolysin; virus antigen; virus envelope; virus infection mechanism; virus protein; virus replication

The influenza virus haemagglutinin (HA) glycoprotein is being studied both as a prototype membrane surface molecule and as a functional component of a viral envelope. X-ray crystallographic studies of the HA from the human, 1968 Hong Kong virus strain produced atomic models from which chemically detailed conclusions about virus functions can be deduced. The detail of these models also permits the design of biochemical, recombinant DNA, and cell biological experiments on the mechanisms of the viral activities. A long-term goal is to develop strategies to intervene in the viral processes to prevent infection. How the virus binds to cells is being studied by X-ray structural analysis of complexes between the HA and synthetic receptor analogs and with complexes between sialocides and affinity mutants of the HA. The structure of the HA from an animal influenza virus Duck/Ukraine/63 the progenitor of the 1968 human Hong Kong strain will be determined. The energetics of the receptor binding interactions are being measured in parallel with X-ray experiments by NMR. Recombinant DNA methods are being used to create site-directed mutations in the interacting residues and to provide quantities of novel molecular species for NMR and X- ray studies. The mechanism of membrane-fusion by which many enveloped animal virus enter cells is being studied by structural analysis of a fusion active and precursor, inactive form of the HA. The structure of membrane fusion mutants and a second fusion active glycoprotein from Influenza C virus are also being studied.

流感病毒血凝素（HA）糖蛋白正在 研究了作为原型膜表面分子的研究 病毒包膜的功能成分。 X射线晶体学 1968年香港病毒菌株对HA的研究 产生的原子模型化学详细的结论 关于病毒功能可以推导。 这些模型的细节 还允许设计生化，重组DNA和细胞 关于病毒活性机制的生物学实验。 一个长期目标是制定策略来干预 预防感染的病毒过程。 X射线结构研究了病毒与细胞的结合 HA和合成受体之间的复合物分析 类似物和唾液酸和亲和力之间的复合物 HA的突变体。 来自动物的HA的结构 流感病毒鸭/乌克兰/63 1968年人类的祖先 将确定香港菌株。 的能量学 受体结合相互作用正在与 NMR进行X射线实验。 重组DNA方法正在使用 在相互作用的残基中创建定点突变，并 为NMR和X-提供数量的新分子物种 射线研究。 膜融合的机制，许多包裹动物的动物 病毒进入细胞正在通过对A的结构分析进行研究 融合活性和前体，HA的非活性形式。 这 膜融合突变体的结构和第二个融合活性 还研究了流感病毒的糖蛋白。