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

Authors
Xie, Q.
Spear, J.
Noble, A.
Sousa, D.
Meyer, N.
Davulcu, O.
Zhang, F.
Stagg, S.
Chapman, M.
ORCID
https://orcid.org/0000-0003-2219-5833
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Issue Date
2017
Keywords
Biology , Chemistry and chemical biology , Chemical and biological engineering , Biomedical engineering
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Terms of Use
Attribution-NonCommercial-NoDerivs 3.0 United States
CC BY-NC-ND : this license allows reusers to copy and distribute the material in any medium or format in unadapted form only, for noncommercial purposes only, and only so long as attribution is given to the creator.
Full Citation
The 2.8 Å Electron Microscopy Structure of Adeno-Associated Virus-DJ Bound by a Heparanoid Pentasaccharide Q. Xie, J. Spear, A. Noble, D. Sousa, N. Meyer, O. Davulcu, F. Zhang, R. Linhardt, S. Stagg, M. Chapman, Molecular Therapy - Methods & Clinical Development, 5, 1-12, 2017.
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.
Description
Molecular Therapy - Methods & Clinical Development, 5, 1-12
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Department
The Linhardt Research Labs.
The Shirley Ann Jackson, Ph.D. Center for Biotechnology and Interdisciplinary Studies (CBIS)
Publisher
Elsevier
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The Linhardt Research Labs Online Collection
Rensselaer Polytechnic Institute, Troy, NY
https://harc.rpi.edu/
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A full text version is available in DSpace@RPI
CC BY — Creative Commons Attribution-NonCommercial-NoDerivatives