6U3Q

The atomic structure of a human adeno-associated virus capsid isolate (AAVhu69/AAVv66)

This is a non-PDB format compatible entry.

Summary for 6U3Q

• Entry DOI: 10.2210/pdb6u3q/pdb
• EMDB information: 20630
• Descriptor: Capsid protein VP1 (1 entity in total)
• Functional Keywords: adeno-associated virus, aav, virus
• Biological source: Adeno-associated virus
• Total number of polymer chains: 60
• Total formula weight: 4909381.86

Authors

Hsu, H.-L.,Brown, A.,Loveland, A.,Tai, P.,Korostelev, A.,Gao, G. (deposition date: 2019-08-22, release date: 2020-05-27, Last modification date: 2024-03-20)

Primary citation

Hsu, H.L.,Brown, A.,Loveland, A.B.,Lotun, A.,Xu, M.,Luo, L.,Xu, G.,Li, J.,Ren, L.,Su, Q.,Gessler, D.J.,Wei, Y.,Tai, P.W.L.,Korostelev, A.A.,Gao, G.
Structural characterization of a novel human adeno-associated virus capsid with neurotropic properties.
Nat Commun, 11:3279-3279, 2020

PubMed Abstract: Recombinant adeno-associated viruses (rAAVs) are currently considered the safest and most reliable gene delivery vehicles for human gene therapy. Three serotype capsids, AAV1, AAV2, and AAV9, have been approved for commercial use in patients, but they may not be suitable for all therapeutic contexts. Here, we describe a novel capsid identified in a human clinical sample by high-throughput, long-read sequencing. The capsid, which we have named AAVv66, shares high sequence similarity with AAV2. We demonstrate that compared to AAV2, AAVv66 exhibits enhanced production yields, virion stability, and CNS transduction. Unique structural properties of AAVv66 visualized by cryo-EM at 2.5-Å resolution, suggest that critical residues at the three-fold protrusion and at the interface of the five-fold axis of symmetry likely contribute to the beneficial characteristics of AAVv66. Our findings underscore the potential of AAVv66 as a gene therapy vector.

PubMed: 32606306
DOI: 10.1038/s41467-020-17047-1

Experimental method

ELECTRON MICROSCOPY (2.46 Å)