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2.8 Angstrom Electron Microscopy Structure Of Adeno-associated Virus-dj Bound By A Heparinoid Pentasaccharide

Title: The 2.8 Angstrom Electron Microscopy Structure Of Adeno-associated Virus-dj Bound By A Heparinoid Pentasaccharide.
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Name(s): Xie, Qing, author
Spear, John M., author
Noble, Alex J., author
Sousa, Duncan R., author
Meyer, Nancy L., author
Davulcu, Omar, author
Zhang, Fuming, author
Linhardt, Robert J., author
Stagg, Scott M., author
Chapman, Michael S., author
Type of Resource: text
Genre: Journal Article
Text
Journal Article
Date Issued: 2017-06
Physical Form: computer
online resource
Extent: 1 online resource
Language(s): English
Abstract/Description: Atomic structures of adeno-associated virus (AAV)-DJ, alone and in complex with fondaparinux, have been determined by cryoelectron microscopy at 3 angstrom 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 multimodal 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.
Identifier: FSU_libsubv1_wos_000406299600001 (IID), 10.1016/j.omtm.2017.02.004 (DOI)
Keywords: complex, cryo-em structure, cryoelectron microscopy, gene-therapy vector, heparan-sulfate, oligosaccharide receptor, resolution, serotype 3b aav-3b, single-particle reconstructions, type-2 capsids
Publication Note: The publisher's version of record is available at https://doi.org/10.1016/j.omtm.2017.02.004
Persistent Link to This Record: http://purl.flvc.org/fsu/fd/FSU_libsubv1_wos_000406299600001
Owner Institution: FSU
Is Part Of: Molecular Therapy-Methods & Clinical Development.
2329-0501
Issue: vol. 5

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Xie, Q., Spear, J. M., Noble, A. J., Sousa, D. R., Meyer, N. L., Davulcu, O., … Chapman, M. S. (2017). The 2.8 Angstrom Electron Microscopy Structure Of Adeno-associated Virus-dj Bound By A Heparinoid Pentasaccharide. Molecular Therapy-Methods & Clinical Development. Retrieved from http://purl.flvc.org/fsu/fd/FSU_libsubv1_wos_000406299600001