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-Structure paper
| タイトル | Structural basis for Rep-mediated adeno-associated virus packaging. |
|---|---|
| ジャーナル・号・ページ | Cell Rep, Vol. 45, Issue 3, Page 117044, Year 2026 |
| 掲載日 | 2026年3月5日 |
著者 | Victoria Xu / Aiysha McInnes / Matthew Wake / Marta Acebrón-García-de-Eulate / Joseph D Barritt / Doryen Bubeck / Sarah L Rouse / ![]() |
| PubMed 要旨 | Adeno-associated viruses (AAVs) are parvoviruses utilized as gene therapy vectors. However, the AAV packaging mechanism is unresolved at the molecular level, creating a bottleneck for vector ...Adeno-associated viruses (AAVs) are parvoviruses utilized as gene therapy vectors. However, the AAV packaging mechanism is unresolved at the molecular level, creating a bottleneck for vector manufacturing, safety, and efficacy. Here, cryo-EM structures of the Rep helicase packaging motor in complex with the packaging marker DNA (ITR) and the Rep-AAV8 capsid complex are presented. Rep-ITR complexes reveal dynamic oligomeric states on the DNA, elucidating the strand separation mechanism coupled to its ATPase cycle. We observe Rep preferentially bound to empty capsids, with a binding interface likely conserved across the virus family. This complex also unveils a cryptic capsid ATP-binding site which, alongside Rep binding, triggers structural rearrangements priming the capsid for packaging. Collectively, these findings advance the understanding of Rep-mediated packaging, with significant implications for parvovirus virology and viral vector design. |
リンク | Cell Rep / PubMed:41790558 |
| 手法 | EM (単粒子) |
| 解像度 | 1.88 - 3.08 Å |
| 構造データ | EMDB-54050, PDB-9rm5: ![]() EMDB-54181: Consensus map of heptameric Rep40-dsDNA (ITR) in presence of ATPyS ![]() EMDB-54182: Focused map of 3 subunits of Rep40 +dsDNA (ITR) in complex with ATPgS ![]() EMDB-54183: Focused map of 4 subunits of heptameric Rep40-dsDNA (ITR) in complex with ATPgS EMDB-54184, PDB-9rqt: EMDB-54195, PDB-9rrs: EMDB-54328, PDB-9rwg: ![]() EMDB-54403: Consensus map of Hexameric AAV2 Rep40-dsDNA (ITR) duplex complex in presence of ATPyS EMDB-54416, PDB-9s0n: EMDB-54429, PDB-9s10: |
| 化合物 | ![]() ChemComp-AGS: ![]() ChemComp-MG: ![]() ChemComp-ADP: ![]() ChemComp-HOH: |
| 由来 |
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キーワード | DNA BINDING PROTEIN / Helicase / Adeno-associated Virus / AAA+ ATPase / VIRUS / AAV |
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adeno-associated virus 2 (アデノ随伴ウイルス)
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