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| Title | The 2.8 Å Electron Microscopy Structure of Adeno-Associated Virus-DJ Bound by a Heparinoid Pentasaccharide. |
|---|---|
| Journal, issue, pages | Mol Ther Methods Clin Dev, Vol. 5, Page 1-12, Year 2017 |
| Publish date | Jun 16, 2017 |
 Authors | Qing Xie / John M Spear / Alex J Noble / Duncan R Sousa / Nancy L Meyer / Omar Davulcu / Fuming Zhang / Robert J Linhardt / Scott M Stagg / Michael S Chapman /  |
| 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 ...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. |
 External links | Mol Ther Methods Clin Dev / PubMed:28480299 / PubMed Central |
| Methods | EM (single particle) |
| Resolution | 2.8 Å |
| Structure data | |
| Chemicals |  ChemComp-HOH: |
| Source |
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 Keywords |  VIRUS LIKE PARTICLE / glycan / receptor / attachment |
