STRUCTURE/FUNCTION ANALYSIS OF THE HIV ENV GENE PRODUCT

HIV ENV 基因产物的结构/功能分析

• 批准号: 8172360
• 负责人: Eric Hunter
• 金额: $ 5.48万
• 依托单位: EMORY UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-05-01 至 2011-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8172360
• 关键词: Amino Acids; Area; Arginine; Biological Process; C-terminal; Cell fusion; Cell membrane; Cells; Charge; Complex; Computer Retrieval of Information on Scientific Projects Database; Cytoplasmic Tail; Funding; Glycine; Glycoproteins; Grant; HIV; Head; Human; Institution; Intracellular Transport; Investigation; Lipids; Lysine; Mediating; Membrane; Membrane Fusion; Modeling; Play; Proteins; Research; Research Personnel; Resources; Role; SIV; Series; Side; Source; Structure; Terminator Codon; Tryptophan; United States National Institutes of Health; Viral; Viral Pathogenesis; Virion; Virus; Virus Assembly; Virus Diseases; base; env Gene Products; mutant

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Three broad areas of investigation have been pursued: + Characterizing the role of the tryptophan-rich membrane-proximal (TRMP) domain of gp41 in Env-mediated membrane fusion and glycoprotein incorporation into virus. + Analyzing the topology and structural requirements of the gp41 membrane-spanning domain for virus assembly and entry. + Determining the role of sequences within the cytoplasmic domain (CD) of HIV Env in intracellular transport, and viral pathogenesis. The membrane-spanning domain (MSD) of the envelope (Env) glycoprotein from human (HIV) and simian immunodeficiency viruses plays a key role in anchoring the Env complex into the viral membrane but also contributes to its biological function in fusion and virus entry. In HIV type 1 (HIV-1), it has been predicted to span 27 amino acids, from lysine residue 681 to arginine 707, and encompasses an internal arginine at residue 694. By examining a series of C-terminal-truncation mutants of the HIV-1 gp41 glycoprotein that substituted termination codons for amino acids 682 to 708, we have shown that this entire region is required for efficient viral infection of target cells. Truncation to the arginine at residue 694 resulted in an Env complex that was secreted from the cells. In contrast, a region from residues 681 to 698, which contains highly conserved hydrophobic residues and glycine motifs and extends 4 amino acids beyond 694R, can effectively anchor the protein in the membrane, allow efficient transport to the plasma membrane, and mediate wild-type levels of cell-cell fusion. However, these fusogenic truncated Env mutants are inefficiently incorporated into budding virions. Based on the analysis of these mutants, a "snorkeling" model, in which the flanking charged amino acid residues at 681 and 694 are buried in the lipid while their side chains interact with polar head groups, is proposed for the HIV-1 MSD.

该副本是利用众多研究子项目之一 由NIH/NCRR资助的中心赠款提供的资源。子弹和 调查员（PI）可能已经从其他NIH来源获得了主要资金， 因此可以在其他清晰的条目中代表。列出的机构是 对于中心，这不一定是调查员的机构。 已进行了三个广泛的调查领域： +表征GP41在Env介导的膜融合中的富含色氨酸膜 - 透明膜（TRMP）结构域的作用，并掺入病毒中。 +分析用于病毒组装和进入的gp41膜跨膜结构域的拓扑和结构要求。 +确定HIV Env的细胞质结构域（CD）在细胞内转运和病毒发病机理中的作用。 来自人类（HIV）和邻近的免疫缺陷病毒的包膜（ENV）糖蛋白的膜跨膜结构域（MSD）在将ENV复合物锚定在病毒膜中起着关键作用，但也有助于其在融合和病毒进入中的生物学功能。在HIV 1型（HIV-1）中，已经预计它将跨越27个氨基酸，从赖氨酸残基681到精氨酸707，并包括在残基694处的内部精氨酸。有效的靶细胞病毒感染所必需的。在残基694处的精氨酸截断导致了一个从细胞分泌的ENV复合物。 相反，残基681至698的区域包含高度保守的疏水残基和甘氨酸基序，并将4个氨基酸延伸到694R以上，可以有效地锚定膜中的蛋白质，使得有效地转运到质膜膜，并介导细胞纤维型野生型野生型野生型。但是，这些融合截断的ENV突变体被低效地纳入了萌芽的病毒体中。 基于对这些突变体的分析，一种“浮潜”模型，其中提出了HIV-1 MSD的侧链与极性头部相互作用的侧翼681和694的侧链氨基酸残基。