3J1S

Structure of adeno-associated virus-2 in complex with neutralizing monoclonal antibody A20

Summary for 3J1S

• Entry DOI: 10.2210/pdb3j1s/pdb
• Related: 1LP3
• EMDB information: 5424
• Descriptor: A20 light chain, A20 heavy chain, Capsid protein VP1 (3 entities in total)
• Functional Keywords: epitope, fab, gene therapy, virus-immune system complex, virus/immune system
• Biological source: Mus musculus (mouse); More
• Total number of polymer chains: 3
• Total formula weight: 106153.90

Authors

Chapman, M.S.,McCraw, D.M. (deposition date: 2012-05-23, release date: 2012-06-06, Last modification date: 2024-10-30)

Primary citation

McCraw, D.M.,O'Donnell, J.K.,Taylor, K.A.,Stagg, S.M.,Chapman, M.S.
Structure of adeno-associated virus-2 in complex with neutralizing monoclonal antibody A20.
Virology, 431:40-49, 2012

PubMed Abstract: The use of adeno-associated virus (AAV) as a gene therapy vector is limited by the host neutralizing immune response. The cryo-electron microscopy (EM) structure at 8.5Å resolution is determined for a complex of AAV-2 with the Fab' fragment of monoclonal antibody (MAb) A20, the most extensively characterized AAV MAb. The binding footprint is determined through fitting the cryo-EM reconstruction with a homology model following sequencing of the variable domain, and provides a structural basis for integrating diverse prior epitope mappings. The footprint extends from the previously implicated plateau to the side of the spike, and into the conserved canyon, covering a larger area than anticipated. Comparison with structures of binding and non-binding serotypes indicates that recognition depends on a combination of subtle serotype-specific features. Separation of the neutralizing epitope from the heparan sulfate cell attachment site encourages attempts to develop immune-resistant vectors that can still bind to target cells.

PubMed: 22682774
DOI: 10.1016/j.virol.2012.05.004

Experimental method

ELECTRON MICROSCOPY (8.5 Å)