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| ==The structure of AAVrh32.33, a Novel Gene Delivery Vector== | | ==The structure of AAVrh32.33, a Novel Gene Delivery Vector== |
| <StructureSection load='4iov' size='340' side='right' caption='[[4iov]], [[Resolution|resolution]] 3.50Å' scene=''> | | <StructureSection load='4iov' size='340' side='right'caption='[[4iov]], [[Resolution|resolution]] 3.50Å' scene=''> |
| == Structural highlights == | | == Structural highlights == |
| <table><tr><td colspan='2'>[[4iov]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Adeno-associated_virus Adeno-associated virus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4IOV OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4IOV FirstGlance]. <br> | | <table><tr><td colspan='2'>[[4iov]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Adeno-associated_virus Adeno-associated virus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4IOV OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4IOV FirstGlance]. <br> |
| </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=D5M:2-DEOXYADENOSINE-5-MONOPHOSPHATE'>D5M</scene></td></tr> | | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 3.5Å</td></tr> |
| <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">Adeno associated virus Rh32-33 VP1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=272636 Adeno-associated virus])</td></tr> | | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=D5M:2-DEOXYADENOSINE-5-MONOPHOSPHATE'>D5M</scene></td></tr> |
| <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4iov FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4iov OCA], [http://pdbe.org/4iov PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4iov RCSB], [http://www.ebi.ac.uk/pdbsum/4iov PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4iov ProSAT]</span></td></tr> | | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=4iov FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4iov OCA], [https://pdbe.org/4iov PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4iov RCSB], [https://www.ebi.ac.uk/pdbsum/4iov PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4iov ProSAT]</span></td></tr> |
| </table> | | </table> |
| <div style="background-color:#fffaf0;">
| | == Function == |
| == Publication Abstract from PubMed == | | [https://www.uniprot.org/uniprot/B4Y891_9VIRU B4Y891_9VIRU] |
| The Adeno-associated viruses (AAVs) are being developed as gene delivery vectors for therapeutic clinical applications. However, the host antibody immune response directed against their capsid, prevalent in approximately 40-70% of the general population, depending on serotype, negatively impacts efficacy. AAVrh32.33, a novel vector developed from rhesus macaques isolates, has significantly lower seroprevalence in human populations compared to AAV2 and AAV8, which are both in clinical use. To better understand the capsid determinants of this differential immune response to AAVrh32.33, its structure was determined by X-ray crystallography to 3.5A resolution. The capsid viral protein (VP) structure conserves the eight-stranded beta-barrel core and alphaA helix reported for other parvoviruses and the distinct capsid surface topology of the AAVs: a depression at the icosahedral twofold axis, three protrusions surrounding the threefold axis, and a depression surround a cylindrical channel at the fivefold axis. A comparison to AAV2, AAV4, and AAV8, to which AAVrh32.33 shares approximately 61%, approximately 81%, and approximately 63% identity, respectively, identified differences in previously defined AAV VP structurally variable regions (VR-1 to VR-IX) which function as receptor attachment, transduction efficiency, and/or antigenic determinants. This structure thus provides a 3D platform for capsid engineering in ongoing efforts to develop AAVrh32.33, as well as other AAV serotypes, for tissue targeted gene-therapy applications with vectors that can evade pre-existing antibody responses against the capsid. These features are required for full clinical realization of the promising AAV gene delivery system.
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| The structure of AAVrh32.33, a novel gene delivery vector.,Mikals K, Nam HJ, Van Vliet K, Vandenberghe LH, Mays LE, McKenna R, Wilson JM, Agbandje-McKenna M J Struct Biol. 2014 May;186(2):308-17. doi: 10.1016/j.jsb.2014.03.020. Epub 2014 , Apr 2. PMID:24704217<ref>PMID:24704217</ref>
| | ==See Also== |
| | | *[[Virus coat proteins 3D structures|Virus coat proteins 3D structures]] |
| From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
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| </div>
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| <div class="pdbe-citations 4iov" style="background-color:#fffaf0;"></div>
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| == References == | |
| <references/>
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| __TOC__ | | __TOC__ |
| </StructureSection> | | </StructureSection> |
| [[Category: Adeno-associated virus]] | | [[Category: Adeno-associated virus]] |
| [[Category: Agbandje-McKenna, M]] | | [[Category: Large Structures]] |
| [[Category: Mays, L E]] | | [[Category: Agbandje-McKenna M]] |
| [[Category: McKenna, R]] | | [[Category: Mays LE]] |
| [[Category: Mikalism, K]] | | [[Category: McKenna R]] |
| [[Category: Nam, H J]] | | [[Category: Mikalism K]] |
| [[Category: Vandenberghe, L H]] | | [[Category: Nam H-J]] |
| [[Category: Wilson, J]]
| | [[Category: Van vilet K]] |
| [[Category: Vilet, K Van]]
| | [[Category: Vandenberghe LH]] |
| [[Category: Beta barrel icosahedral capsid]] | | [[Category: Wilson J]] |
| [[Category: Plasma]] | |
| [[Category: Viral capsid]]
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| [[Category: Virus]]
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