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-Structure paper
| タイトル | Oligomeric HIV-1 integrase structures reveal functional plasticity for intasome assembly and RNA binding. |
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| ジャーナル・号・ページ | Nat Commun, Vol. 16, Issue 1, Page 9430, Year 2025 |
| 掲載日 | 2025年10月24日 |
著者 | Tao Jing / Zelin Shan / Tung Dinh / Avik Biswas / Sooin Jang / Juliet Greenwood / Min Li / Zeyuan Zhang / Gennavieve Gray / Hye Jeong Shin / Bo Zhou / Dario Passos / Timothy S Strutzenberg / Sriram Aiyer / Leonardo Andrade / Yuxuan Zhang / Zhen Li / Robert Craigie / Alan N Engelman / Mamuka Kvaratskhelia / Dmitry Lyumkis / ![]() |
| PubMed 要旨 | 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. ...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. |
リンク | Nat Commun / PubMed:41136407 / PubMed Central |
| 手法 | EM (単粒子) |
| 解像度 | 4.0 - 8.0 Å |
| 構造データ | EMDB-44962, PDB-9bw9: ![]() EMDB-45103: Consensus map of NL4-3 WT HIV-1 intasome ![]() EMDB-45104: Top half of NL4-3 WT HIV-1 intasome ![]() EMDB-45150: Bottom half of NL4-3 WT HIV-1 intasome EMDB-45151, PDB-9c29: |
| 化合物 | ![]() ChemComp-MG: |
| 由来 |
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キーワード | VIRAL PROTEIN / protein complex / hydrolase / VIRAL PROTEIN/DNA / VIRAL PROTEIN-DNA complex |
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著者
リンク







HIV type 1 (ヒト免疫不全ウイルス)
homo sapiens (ヒト)
キーワード