Structure and function of Hepacivirus envelope glycoprotein

肝炎病毒包膜糖蛋白的结构和功能

• 批准号: 9084122
• 负责人: Mansun Law
• 金额: $ 62.56万
• 依托单位: SCRIPPS RESEARCH INSTITUTE, THE
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-02-15 至 2021-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9084122
• 关键词: Adopted; Affect; Alanine; Amino Acids; Biology; CD81 gene; Cells; Chimeric Proteins; Cleaved cell; Complex; Crystallization; Data; Disulfides; Drug Design; Elements; Engineering; Epitopes; Flavivirus; Genotype; Glycoproteins; Goals; Hepacivirus; Hepatitis C Vaccine; Hepatitis C virus; Human; In Vitro; Individual; Length; Libraries; Link; Malignant neoplasm of liver; Maps; Mediating; Membrane Fusion; Methods; Molecular Chaperones; Monoclonal Antibodies; Mutagenesis; Mutation; N-terminal; Pan Genus; Patients; Peptides; Pestivirus; Pharmaceutical Preparations; Population; Proteins; Public Health; Reagent; Recombinants; Reporting; Resolution; Roentgen Rays; Role; Scanning; Shotguns; Source; Structure; Structure-Activity Relationship; Surface; System; Techniques; Testing; Vaccine Design; Vaccines; Viral; Viral Proteins; Virion; Virus; Virus Replication; base; cell assembly; chronic liver disease; combat; design; env Glycoproteins; flexibility; follow-up; glycoprotein structure; immunological intervention; improved; insight; monomer; mutant; neutralizing antibody; novel; pathogen; programs; protein expression; protein folding; protein function; protein purification; protein structure; public health relevance; receptor; receptor binding; recombinant virus; virus envelope

 DESCRIPTION (provided by applicant): Hepatitis C virus (HCV) chronically infects 2-3% of the global population, predisposing the patients to chronic liver diseases and liver cancer. To combat this major public health threat, a detailed understanding of the viral molecules will greatly facilitate vaccine and anti-viral drug design. The HCV envelope glycoproteins (Env), comprised of heterodimers of the E1 and E2 viral glycoproteins, are important for viral attachment and entry into host cells, and the assembly of infectious virus particles. The E1 and E2 glycoproteins are potential targets for pharmacological and immunological intervention. The goals of this application are to determine the high-resolution crystal structure of HCV envelope glycoproteins, and the functions of the glycoproteins at the amino acid level. The results will aid the rational design of anti-viral drugs and vaccines, and to understand the viral entry mechanism. The specific aims are (i) to determine the high-resolution crystal structure of HCV E2 and E2:receptor complex; (ii) to study the roles of individual amino acid residues in protein functions by a shotgun mutagenesis approach; and (iii) to determine the high-resolution crystal structures of HCV E1 and E1E2 complex.

 描述（由申请人提供）：丙型肝炎病毒（HCV）慢性感染全球2-3%的人口，使患者易患慢性肝病和肝癌。为了应对这一重大的公共卫生威胁，对病毒分子的详细了解将极大地促进疫苗和抗病毒药物的设计。HCV包膜糖蛋白（Env）由E1和E2病毒糖蛋白的异源二聚体组成，对于病毒附着和进入宿主细胞以及感染性病毒颗粒的组装是重要的。E1和E2糖蛋白是药理学和免疫学干预的潜在靶点。本申请的目的是确定HCV包膜糖蛋白的高分辨率晶体结构，以及在氨基酸水平上糖蛋白的功能。结果将有助于 抗病毒药物和疫苗的合理设计，以及了解病毒进入机制。具体目的是（i）确定HCV E2和E2：受体复合物的高分辨率晶体结构;（ii）通过鸟枪诱变方法研究单个氨基酸残基在蛋白质功能中的作用;（iii）确定HCV E1和E1 E2复合物的高分辨率晶体结构。