9C29

Hexadecamer of NL4-3 WT HIV-1 intasome

9C29 の概要

• エントリーDOI: 10.2210/pdb9c29/pdb
• EMDBエントリー: 45151
• 分子名称: Integrase, DNA (5'-D(*AP*CP*TP*GP*CP*TP*AP*GP*AP*GP*AP*TP*TP*TP*TP*CP*CP*CP*G)-3'), DNA (5'-D(P*CP*GP*GP*GP*AP*AP*AP*AP*TP*CP*TP*CP*TP*AP*GP*CP*A)-3'), ... (4 entities in total)
• 機能のキーワード: viral protein, protein complex, viral protein-dna complex, viral protein/dna
• 由来する生物種: HIV-1 06TG.HT008; 詳細
• タンパク質・核酸の鎖数: 20
• 化学式量合計: 538046.15

構造登録者

Lyumkis, D.,Jing, T.,Zhang, Z. (登録日: 2024-05-30, 公開日: 2025-06-25, 最終更新日: 2025-11-05)

主引用文献

Jing, T.,Shan, Z.,Dinh, T.,Biswas, A.,Jang, S.,Greenwood, J.,Li, M.,Zhang, Z.,Gray, G.,Shin, H.J.,Zhou, B.,Passos, D.,Strutzenberg, T.S.,Aiyer, S.,Andrade, L.,Zhang, Y.,Li, Z.,Craigie, R.,Engelman, A.N.,Kvaratskhelia, M.,Lyumkis, D.
Oligomeric HIV-1 integrase structures reveal functional plasticity for intasome assembly and RNA binding.
Nat Commun, 16:9430-9430, 2025

PubMed Abstract: Integrase (IN) performs dual essential roles during HIV-1 replication. During ingress, IN functions within an oligomeric "intasome" assembly to catalyze viral DNA integration into host chromatin. During late stages of infection, tetrameric IN binds viral RNA and orchestrates the condensation of ribonucleoprotein complexes into the capsid core. The molecular architectures of HIV-1 IN assemblies that mediate these distinct events remain unknown. Furthermore, the IN tetramer is an important antiviral target for investigational allosteric IN inhibitors. Here, we determined cryo-EM structures of wildtype HIV-1 IN tetramers and intasome hexadecamers. Our structures unveil a remarkable plasticity that leverages IN C-terminal domains and abutting linkers to assemble functionally distinct oligomeric forms. Alteration of a newly recognized conserved interface revealed that both IN functions track with tetramerization in vitro and during HIV-1 infection. Collectively, our findings reveal how IN plasticity orchestrates its diverse molecular functions and suggest a working model for IN-viral RNA binding. Moreover, our structure of the IN tetramer provides atomic blueprints for the rational development of improved allosteric inhibitors.

PubMed: 41136407
DOI: 10.1038/s41467-025-64479-8

実験手法

ELECTRON MICROSCOPY (8 Å)