9RWG

Pentameric AAV2 Rep40 in complex with AAV8

This is a non-PDB format compatible entry.

Summary for 9RWG

• Entry DOI: 10.2210/pdb9rwg/pdb
• Related: 9RRS
• EMDB information: 54328
• Descriptor: Capsid protein, Protein Rep68, ADENOSINE-5'-DIPHOSPHATE, ... (4 entities in total)
• Functional Keywords: adeno-associated virus, aav, aaa+ atpase, virus
• Biological source: adeno-associated virus 8; More
• Total number of polymer chains: 20
• Total formula weight: 1453609.78

Authors

Rouse, S.L.,Bubeck, D.,Barritt, J.D.,Xu, V.,Wake, M. (deposition date: 2025-07-09, release date: 2026-02-04, Last modification date: 2026-03-18)

Primary citation

Xu, V.,McInnes, A.,Wake, M.,Acebron-Garcia-de-Eulate, M.,Barritt, J.D.,Bubeck, D.,Rouse, S.L.
Structural basis for Rep-mediated adeno-associated virus packaging.
Cell Rep, 45:117044-117044, 2026

PubMed Abstract: 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.

PubMed: 41790558
DOI: 10.1016/j.celrep.2026.117044

Experimental method

ELECTRON MICROSCOPY (2.19 Å)