5UF6

The 2.8 A Electron Microscopy Structure of Adeno-Associated Virus-DJ Bound by a Heparanoid Pentasaccharide

Summary for 5UF6

• Entry DOI: 10.2210/pdb5uf6/pdb
• EMDB information: 6470 8574
• Related PRD ID: PRD_900028
• Descriptor: capsid protein VP1, 2-deoxy-6-O-sulfo-2-(sulfoamino)-alpha-D-glucopyranose-(1-4)-beta-D-glucopyranuronic acid-(1-4)-2-deoxy-3,6-di-O-sulfo-2-(sulfoamino)-alpha-D-glucopyranose-(1-4)-2-O-sulfo-alpha-L-idopyranuronic acid-(1-4)-methyl 2-deoxy-6-O-sulfo-2-(sulfoamino)-alpha-D-glucopyranoside (3 entities in total)
• Functional Keywords: glycan, receptor, attachment, virus like particle
• Biological source: Adeno-associated virus
• Total number of polymer chains: 1
• Total formula weight: 60085.80

Authors

Xie, Q.,Spear, J.M.,Noble, A.J.,Sousa, D.R.,Meyer, N.L.,Davulcu, O.,Zhang, F.,Linhardt, R.J.,Stagg, S.M.,Chapman, M. (deposition date: 2017-01-03, release date: 2017-05-24, Last modification date: 2024-03-06)

Primary citation

Xie, Q.,Spear, J.M.,Noble, A.J.,Sousa, D.R.,Meyer, N.L.,Davulcu, O.,Zhang, F.,Linhardt, R.J.,Stagg, S.M.,Chapman, M.S.
The 2.8 angstrom Electron Microscopy Structure of Adeno-Associated Virus-DJ Bound by a Heparinoid Pentasaccharide.
Mol Ther Methods Clin Dev, 5:1-12, 2017

PubMed Abstract: Atomic structures of adeno-associated virus (AAV)-DJ, alone and in complex with fondaparinux, have been determined by cryoelectron microscopy at 3 Å resolution. The gene therapy vector, AAV-DJ, is a hybrid of natural serotypes that was previously derived by directed evolution, selecting for hepatocyte entry and resistance to neutralization by human serum. The structure of AAV-DJ differs from that of parental serotypes in two regions where neutralizing antibodies bind, so immune escape appears to have been the primary driver of AAV-DJ's directed evolution. Fondaparinux is an analog of cell surface heparan sulfate to which several AAVs bind during entry. Fondaparinux interacts with viral arginines at a known heparin binding site, without the large conformational changes whose presence was controversial in low-resolution imaging of AAV2-heparin complexes. The glycan density suggests multi-modal binding that could accommodate sequence variation and multivalent binding along a glycan polymer, consistent with a role in attachment, prior to more specific interactions with a receptor protein mediating entry.

PubMed: 28480299
DOI: 10.1016/j.omtm.2017.02.004

Experimental method

ELECTRON MICROSCOPY (2.8 Å)