5HGP

Hexameric HIV-1 CA in complex with hexacarboxybenzene

5HGP の概要

• エントリーDOI: 10.2210/pdb5hgp/pdb
• 分子名称: Capsid protein P24, BENZENE HEXACARBOXYLIC ACID (3 entities in total)
• 機能のキーワード: capsid, viral protein
• 由来する生物種: Human immunodeficiency virus type 1 (HIV-1)
• 細胞内の位置: Gag polyprotein: Host cell membrane; Lipid- anchor . Matrix protein p17: Virion membrane; Lipid- anchor . Capsid protein p24: Virion . Nucleocapsid protein p7: Virion : P12493
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 25803.44

構造登録者

Jacques, D.A.,James, L.C. (登録日: 2016-01-08, 公開日: 2016-10-19, 最終更新日: 2024-10-09)

主引用文献

Jacques, D.A.,McEwan, W.A.,Hilditch, L.,Price, A.J.,Towers, G.J.,James, L.C.
HIV-1 uses dynamic capsid pores to import nucleotides and fuel encapsidated DNA synthesis.
Nature, 536:349-353, 2016

PubMed Abstract: During the early stages of infection, the HIV-1 capsid protects viral components from cytosolic sensors and nucleases such as cGAS and TREX, respectively, while allowing access to nucleotides for efficient reverse transcription. Here we show that each capsid hexamer has a size-selective pore bound by a ring of six arginine residues and a 'molecular iris' formed by the amino-terminal β-hairpin. The arginine ring creates a strongly positively charged channel that recruits the four nucleotides with on-rates that approach diffusion limits. Progressive removal of pore arginines results in a dose-dependent and concomitant decrease in nucleotide affinity, reverse transcription and infectivity. This positively charged channel is universally conserved in lentiviral capsids despite the fact that it is strongly destabilizing without nucleotides to counteract charge repulsion. We also describe a channel inhibitor, hexacarboxybenzene, which competes for nucleotide binding and efficiently blocks encapsidated reverse transcription, demonstrating the tractability of the pore as a novel drug target.

PubMed: 27509857
DOI: 10.1038/nature19098

実験手法

X-RAY DIFFRACTION (1.95 Å)