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TitleThe 2.8 Å Electron Microscopy Structure of Adeno-Associated Virus-DJ Bound by a Heparinoid Pentasaccharide.
Journal, issue, pagesMol Ther Methods Clin Dev, Vol. 5, Page 1-12, Year 2017
Publish dateJun 16, 2017
AuthorsQing 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 AbstractAtomic 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 linksMol Ther Methods Clin Dev / PubMed:28480299 / PubMed Central
MethodsEM (single particle)
Resolution2.8 Å
Structure data

8574

5uf6

EMDB-8574: Single particle reconstruction of chimeric adeno-associated virus-DJ with a Heparanoid Pentasaccharide
PDB-5uf6: The 2.8 A Electron Microscopy Structure of Adeno-Associated Virus-DJ Bound by a Heparanoid Pentasaccharide
Method: EM (single particle) / Resolution: 2.8 Å

Chemicals

ChemComp-HOH:
WATER

Source
  • adeno-associated virus
KeywordsVIRUS LIKE PARTICLE / glycan / receptor / attachment

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