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Line 3: |
| <SX load='6v1g' size='340' side='right' viewer='molstar' caption='[[6v1g]], [[Resolution|resolution]] 2.98Å' scene=''> | | <SX load='6v1g' size='340' side='right' viewer='molstar' caption='[[6v1g]], [[Resolution|resolution]] 2.98Å' scene=''> |
| == Structural highlights == | | == Structural highlights == |
| <table><tr><td colspan='2'>[[6v1g]] is a 60 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=6V1G OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6V1G FirstGlance]. <br> | | <table><tr><td colspan='2'>[[6v1g]] is a 60 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=6V1G OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6V1G FirstGlance]. <br> |
| </td></tr><tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">cap ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=272636 Adeno-associated virus])</td></tr> | | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 2.98Å</td></tr> |
| <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=6v1g FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6v1g OCA], [http://pdbe.org/6v1g PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6v1g RCSB], [http://www.ebi.ac.uk/pdbsum/6v1g PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6v1g 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=6v1g FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6v1g OCA], [https://pdbe.org/6v1g PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6v1g RCSB], [https://www.ebi.ac.uk/pdbsum/6v1g PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6v1g ProSAT]</span></td></tr> |
| </table> | | </table> |
| <div style="background-color:#fffaf0;">
| | == Function == |
| == Publication Abstract from PubMed == | | [https://www.uniprot.org/uniprot/Q6JC62_9VIRU Q6JC62_9VIRU] |
| Adeno-associated viruses (AAVs) from clade E are often used as vectors in gene delivery applications. This clade includes rhesus isolate 10 (AAVrh.10) and 39 (AAVrh.39) which, unlike representative AAV8, are capable of crossing the blood-brain barrier (BBB) thereby enabling the delivery of therapeutic genes to the CNS. Here the capsid structures of AAV8, AAVrh.10 and AAVrh.39 have been determined by cryo-electron microscopy and three-dimensional image reconstruction to 3.08, 2.75, and 3.39 A resolution, respectively, to enable a direct structural comparison. AAVrh.10 and AAVrh.39 are 98% identical in amino acid sequence but only approximately 93.5% to AAV8. However, the capsid structures of all three viruses are similar with only minor differences observed in the previously described surface variable regions suggesting that the specific residues S269 and N472, absent in AAV8, may confer the ability to cross the BBB in AAVrh.10 and AAVrh.39. Head-to-head comparison of empty and genome-containing particles showed DNA ordered in the previously described nucleotide-binding pocket supporting the suggested role of this pocket in DNA packaging for the Dependoparvovirus The structural characterization of these viruses provides a platform for future vector engineering efforts towards improved gene delivery success with respect to specific tissue targeting, transduction efficiency, antigenicity or receptor retargeting.Importance Recombinant adeno-associated virus vectors (rAAVs), based on AAV8 and AAVrh.10, have been utilized in multiple clinical trials to treat different monogenetic diseases. Closely related AAVrh.39 has also shown promise in vivo As recently attained for other AAV biologics, e.g. Luxturna and Zolgensma, based on AAV2 and AAV9, respectively, the vectors in this study will likely gain FDA approval for commercialization in the near future. The study characterized the capsid structures of these clinical vectors, at atomic resolution using cryo-EM and image reconstruction, for comparative analysis. The analysis suggested two key residues, S269 and N472, as determinants of BBB crossing for AAVrh.10 and AAVrh.39, a feature utilized for CNS delivery of therapeutic genes. The structure information thus provides a platform for engineering to improve receptor retargeting or tissue specificity. These are important challenges in the field that need attention. Capsid structure information also provides knowledge potentially applicable for regulatory product approval.
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| Comparative Analysis of the Capsid Structures of AAVrh.10, AAVrh.39, and AAV8.,Mietzsch M, Barnes C, Hull JA, Chipman P, Xie J, Bhattacharya N, Sousa D, McKenna R, Gao G, Agbandje-McKenna M J Virol. 2019 Dec 11. pii: JVI.01769-19. doi: 10.1128/JVI.01769-19. PMID:31826994<ref>PMID:31826994</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>
| |
| <div class="pdbe-citations 6v1g" style="background-color:#fffaf0;"></div>
| |
| == References == | |
| <references/>
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| __TOC__ | | __TOC__ |
| </SX> | | </SX> |
| [[Category: Adeno-associated virus]] | | [[Category: Adeno-associated virus]] |
| [[Category: Large Structures]] | | [[Category: Large Structures]] |
| [[Category: Agbandje-McKenna, M]] | | [[Category: Agbandje-McKenna M]] |
| [[Category: Mietzsch, M]] | | [[Category: Mietzsch M]] |
| [[Category: Aavrh 10]]
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| [[Category: Capsid]]
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| [[Category: Genome]]
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| [[Category: Nucleotide binding pocket]]
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| [[Category: Virus]]
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