4V86

Structure-function Analysis of Receptor-binding in Adeno-Associated Virus Serotype 6 (AAV-6)

This is a non-PDB format compatible entry.

Summary for 4V86

• Entry DOI: 10.2210/pdb4v86/pdb
• Related: 3SHM
• Descriptor: Capsid protein VP1 (1 entity in total)
• Functional Keywords: beta barrel, virus
• Biological source: Adeno-associated virus - 6
• Total number of polymer chains: 60
• Total formula weight: 3501635.88

Authors

Xie, Q. (deposition date: 2011-09-13, release date: 2014-07-09, Last modification date: 2024-02-28)

Primary citation

Xie, Q.,Lerch, T.F.,Meyer, N.L.,Chapman, M.S.
Structure-function analysis of receptor-binding in adeno-associated virus serotype 6 (AAV-6).
Virology, 420:10-19, 2011

PubMed Abstract: Crystal structures of the AAV-6 capsid at 3Å reveal a subunit fold homologous to other parvoviruses with greatest differences in two external loops. The electrostatic potential suggests that receptor-attachment is mediated by four residues: Arg(576), Lys(493), Lys(459) and Lys(531), defining a positively charged region curving up from the valley between adjacent spikes. It overlaps only partially with the receptor-binding site of AAV-2, and the residues endowing the electrostatic character are not homologous. Mutational substitution of each residue decreases heparin affinity, particularly Lys(531) and Lys(459). Neither is conserved among heparin-binding serotypes, indicating that diverse modes of receptor attachment have been selected in different serotypes. Surface topology and charge are also distinct at the shoulder of the spike, where linear epitopes for AAV-2's neutralizing monoclonal antibody A20 come together. Evolutionarily, selection of changed side-chain charge may have offered a conservative means to evade immune neutralization while preserving other essential functionality.

PubMed: 21917284
DOI: 10.1016/j.virol.2011.08.011

Experimental method

X-RAY DIFFRACTION (3.003 Å)