2ESX

The structure of the V3 region within gp120 of JR-FL HIV-1 strain (minimized average structure)

2ESX の概要

• エントリーDOI: 10.2210/pdb2esx/pdb
• 関連するPDBエントリー: 2ESZ
• 分子名称: Envelope polyprotein GP160 (1 entity in total)
• 機能のキーワード: hiv-1, jr-fl, v3, 447-52d, antibody, viral protein
• 由来する生物種: Human immunodeficiency virus 1
• 細胞内の位置: Transmembrane protein gp41: Virion membrane; Single-pass type I membrane protein. Surface protein gp120: Virion membrane; Peripheral membrane protein: P20871
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 2108.40

構造登録者

Rosen, O.,Sharon, M.,Samson, A.O.,Quadt, S.R.,Anglister, J. (登録日: 2005-10-27, 公開日: 2006-09-19, 最終更新日: 2024-05-22)

主引用文献

Rosen, O.,Sharon, M.,Quadt-Akabayov, S.R.,Anglister, J.
Molecular switch for alternative conformations of the HIV-1 V3 region: Implications for phenotype conversion.
Proc.Natl.Acad.Sci.Usa, 13:13950-13955, 2006

PubMed Abstract: HIV-1 coreceptor usage plays a critical role in virus tropism and pathogenesis. A switch from CCR5- to CXCR4-using viruses occurs during the course of HIV-1 infection and correlates with subsequent disease progression. A single mutation at position 322 within the V3 loop of the HIV-1 envelope glycoprotein gp120, from a negatively to a positively charged residue, was found to be sufficient to switch an R5 virus to an X4 virus. In this study, the NMR structure of the V3 region of an R5 strain, HIV-1(JR-FL), in complex with an HIV-1-neutralizing antibody was determined. Positively charged and negatively charged residues at positions 304 and 322, respectively, oppose each other in the beta-hairpin structure, enabling a favorable electrostatic interaction that stabilizes the postulated R5 conformation. Comparison of the R5 conformation with the postulated X4 conformation of the V3 region (positively charged residue at position 322) reveals that electrostatic repulsion between residues 304 and 322 in X4 strains triggers the observed one register shift in the N-terminal strand of the V3 region. We posit that electrostatic interactions at the base of the V3 beta-hairpin can modulate the conformation and thereby influence the phenotype switch. In addition, we suggest that interstrand cation-pi interactions between positively charged and aromatic residues induce the switch to the X4 conformation as a result of the S306R mutation. The existence of three pairs of identical (or very similar) amino acids in the V3 C-terminal strand facilitates the switch between the R5 and X4 conformations.

PubMed: 16966601
DOI: 10.1073/pnas.0606312103

実験手法

SOLUTION NMR