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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 |
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| Type of Resource: | text | |
| Genre: |
Journal Article Text Journal Article |
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| Date Issued: | 2017-06 | |
| Physical Form: |
computer online resource |
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| 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 | |
| Host Institution: | FSU | |
| Is Part Of: |
Molecular Therapy-Methods & Clinical Development. 2329-0501 |
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| Issue: | vol. 5 |
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
