TOPOGENIC REPERTOIRE OF AIDS VIRUS ENVELOPE GLYCOPROTEIN

艾滋病病毒包膜糖蛋白的拓扑结构库

• 批准号: 3454219
• 负责人: M ABDUL JABBAR
• 金额: $ 8.89万
• 依托单位: UNIVERSITY OF CALIFORNIA LOS ANGELES
• 依托单位国家: 美国
• 财政年份: 1987
• 资助国家: 美国
• 起止时间: 1987-09-30 至 1992-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3454219
• 关键词: AIDS; gene deletion mutation; genetic manipulation; glycoproteins; human immunodeficiency virus; molecular cloning; protein biosynthesis; protein engineering; protein transport; surface antigens; synthetic antigens; virus antigen; virus cytopathogenic effect; virus envelope; virus genetics; virus protein

The envelope glycoprotein of the acquired immune deficiency syndrome (AIDS) virus (also known as LAV, HTLVIII, ARV and HIV) is the major surface antigen against which the neutralizing antibodies are produced in patients infected with the virus. The protein plays a major role in the infection process by providing receptors binding site and by inducing syncytia formation and cytopathic killing of the infected cells. The molecular cloning of the AIDS proviral DNA contributed immensely in assigning the functions for individual genes that might have direct role in the pathogenesis of the virus. The genetically engineered env gene is shown to direct the synthesis of a precursor envelope glycoprotein that is processed and transported to the cell surface indicating the presence of topogenic sequences necessary for transport and targeting o the protein to the cell surface. The goal of this project is to delineate these functional domains involved in protein transport and define their specific role in protein sorting process. I would use cloned DNA encoding the envelope glycoprotein of ARV-2 and make specific mutations in the DNA encoding the carboxyl terminal cytoplasmic region, transmembrane anchor domain as well as the signal region. The mutated genes would be introduced into mammalian cells and the protein products analyzed as to their intracellular transport and localization. The specific deletions (100-130 aa) of the unusually long cytoplasmic region (150 aa) as well as the anchor domain would define the functions of these domains in the intracellular and cell surface transport. Similarly, deletions in the leader (signal) region would define the minimum sequence requirement for translocation and cleavage by signal peptidase. Thus, the mutational analysis of the specific domains of ARV-2 envelope glycoprotein would help elucidate their contribution in the intracellular sorting process.

获得的免疫缺陷的信封糖蛋白 综合征（AIDS）病毒（也称为LAV，HTLVIII，ARV和HIV） 是主要的表面抗原 感染病毒的患者产生抗体。 这 蛋白质通过提供在感染过程中起主要作用 受体结合位点并通过诱导合胞质形成和 受感染细胞的细胞病变杀死。 分子克隆 艾滋病病毒DNA在分配方面做出了巨大贡献 单个基因的功能，可能在 病毒的发病机理。 基因设计的Env基因是 显示用于指导前体包膜糖蛋白的合成 处理并运输到细胞表面，指示 运输和 将O蛋白靶向细胞表面。 目标的目标 项目是描述所涉及的这些功能域 蛋白质转运并定义其在蛋白质分类中的特定作用 过程。 我会使用编码信封的克隆DNA ARV-2的糖蛋白并在DNA中进行特异性突变 编码羧基末端细胞质区域， 跨膜锚域以及信号区域。 这 突变的基因将被引入哺乳动物细胞和 分析了其细胞内转运和 本土化。 异常的特定缺失（100-130 AA） 长细胞质区域（150 aa）以及锚域 将定义细胞内这些域的功能 和细胞表面运输。 同样，领导者的删除 （信号）区域将定义最小序列要求 用于信号肽酶的易位和裂解。 因此， ARV-2包膜特定域的突变分析 糖蛋白将有助于阐明他们在 细胞内分类过程。