2B4J

Structural basis for the recognition between HIV-1 integrase and LEDGF/p75

2B4J の概要

• エントリーDOI: 10.2210/pdb2b4j/pdb
• 関連するPDBエントリー: 1ITG 1K6Y 1z9e
• 分子名称: Integrase (IN), PC4 and SFRS1 interacting protein, PHOSPHATE ION, ... (5 entities in total)
• 機能のキーワード: hiv, integration, transcription, viral protein, recombination
• 由来する生物種: Human immunodeficiency virus 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 : P12497; Nucleus : O75475
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 59524.24

構造登録者

Cherepanov, P.,Ambrosio, A.L.,Rahman, S.,Ellenberger, T.,Engelman, A. (登録日: 2005-09-24, 公開日: 2005-10-25, 最終更新日: 2023-08-23)

主引用文献

Cherepanov, P.,Ambrosio, A.L.,Rahman, S.,Ellenberger, T.,Engelman, A.
Structural basis for the recognition between HIV-1 integrase and transcriptional coactivator p75
Proc.Natl.Acad.Sci.Usa, 102:17308-17313, 2005

PubMed Abstract: Integrase (IN) is an essential retroviral enzyme, and human transcriptional coactivator p75, which is also referred to as lens epithelium-derived growth factor (LEDGF), is the dominant cellular binding partner of HIV-1 IN. Here, we report the crystal structure of the dimeric catalytic core domain of HIV-1 IN complexed to the IN-binding domain of LEDGF. Previously identified LEDGF hotspot residues anchor the protein to both monomers at the IN dimer interface. The principal structural features of IN that are recognized by the host factor are the backbone conformation of residues 168-171 from one monomer and a hydrophobic patch that is primarily comprised of alpha-helices 1 and 3 of the second IN monomer. Inspection of diverse retroviral primary and secondary sequence elements helps to explain the apparent lentiviral tropism of the LEDGF-IN interaction. Because the lethal phenotypes of HIV-1 mutant viruses unable to interact with LEDGF indicate that IN function is highly sensitive to perturbations of the structure around the LEDGF-binding site, we propose that small molecule inhibitors of the protein-protein interaction might similarly disrupt HIV-1 replication.

PubMed: 16260736
DOI: 10.1073/pnas.0506924102

実験手法

X-RAY DIFFRACTION (2.02 Å)