5EU7

Crystal structure of HIV-1 integrase catalytic core in complex with Fab

5EU7 の概要

• エントリーDOI: 10.2210/pdb5eu7/pdb
• 分子名称: Integrase, FAB Heavy Chain, FAB light chain, ... (4 entities in total)
• 機能のキーワード: integrase, fab, hiv, viral protein
• 由来する生物種: Human immunodeficiency virus 1 (HIV-1); 詳細
• 細胞内の位置: Gag-Pol polyprotein: Host cell membrane; Lipid-anchor . Matrix protein p17: Virion membrane; Lipid- anchor . Capsid protein p24: Virion . Nucleocapsid protein p7: Virion . Reverse transcriptase/ribonuclease H: Virion . Integrase: Virion : P04585
• タンパク質・核酸の鎖数: 6
• 化学式量合計: 129823.00

構造登録者

Galilee, M.,Griner, S.L.,Stroud, R.M.,Alian, A. (登録日: 2015-11-18, 公開日: 2016-09-28, 最終更新日: 2024-11-20)

主引用文献

Galilee, M.,Britan-Rosich, E.,Griner, S.L.,Uysal, S.,Baumgartel, V.,Lamb, D.C.,Kossiakoff, A.A.,Kotler, M.,Stroud, R.M.,Marx, A.,Alian, A.
The Preserved HTH-Docking Cleft of HIV-1 Integrase Is Functionally Critical.
Structure, 24:1936-1946, 2016

PubMed Abstract: HIV-1 integrase (IN) catalyzes viral DNA integration into the host genome and facilitates multifunctional steps including virus particle maturation. Competency of IN to form multimeric assemblies is functionally critical, presenting an approach for anti-HIV strategies. Multimerization of IN depends on interactions between the distinct subunit domains and among the flanking protomers. Here, we elucidate an overlooked docking cleft of IN core domain that anchors the N-terminal helix-turn-helix (HTH) motif in a highly preserved and functionally critical configuration. Crystallographic structure of IN core domain in complex with Fab specifically targeting this cleft reveals a steric overlap that would inhibit HTH-docking, C-terminal domain contacts, DNA binding, and subsequent multimerization. While Fab inhibits in vitro IN integration activity, in vivo it abolishes virus particle production by specifically associating with preprocessed IN within Gag-Pol and interfering with early cytosolic Gag/Gag-Pol assemblies. The HTH-docking cleft may offer a fresh hotspot for future anti-HIV intervention strategies.

PubMed: 27692964
DOI: 10.1016/j.str.2016.08.015

実験手法

X-RAY DIFFRACTION (2.64 Å)