3j1s
From Proteopedia
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| - | [[ | + | ==Structure of adeno-associated virus-2 in complex with neutralizing monoclonal antibody A20== |
| + | <StructureSection load='3j1s' size='340' side='right' caption='[[3j1s]], [[Resolution|resolution]] 8.50Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[3j1s]] is a 3 chain structure with sequence from [http://en.wikipedia.org/wiki/Adeno-associated_virus_-_2 Adeno-associated virus - 2] and [http://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3J1S OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3J1S FirstGlance]. <br> | ||
| + | </td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1lp3|1lp3]]</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=3j1s FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3j1s OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3j1s RCSB], [http://www.ebi.ac.uk/pdbsum/3j1s PDBsum]</span></td></tr> | ||
| + | </table> | ||
| + | == Function == | ||
| + | [[http://www.uniprot.org/uniprot/CAPSD_AAV2S CAPSD_AAV2S]] Capsid protein self-assembles to form an icosahedral capsid with a T=1 symmetry, about 22 nm in diameter, and consisting of 60 copies of three size variants of the capsid protein VP1, VP2 and VP3 which differ in their N-terminus. The capsid encapsulates the genomic ssDNA. Binds to host cell heparan sulfate and uses host ITGA5-ITGB1 as coreceptor on the cell surface to provide virion attachment to target cell. This attachment induces virion internalization predominantly through clathrin-dependent endocytosis. Binding to the host receptor also induces capsid rearrangements leading to surface exposure of VP1 N-terminus, specifically its phospholipase A2-like region and putative nuclear localization signal(s). VP1 N-terminus might serve as a lipolytic enzyme to breach the endosomal membrane during entry into host cell and might contribute to virus transport to the nucleus.<ref>PMID:10684294</ref> <ref>PMID:11961250</ref> <ref>PMID:16940508</ref> <ref>PMID:9445046</ref> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | The use of adeno-associated virus (AAV) as a gene therapy vector is limited by the host neutralizing immune response. The cryo-electron microscopy (EM) structure at 8.5A resolution is determined for a complex of AAV-2 with the Fab' fragment of monoclonal antibody (MAb) A20, the most extensively characterized AAV MAb. The binding footprint is determined through fitting the cryo-EM reconstruction with a homology model following sequencing of the variable domain, and provides a structural basis for integrating diverse prior epitope mappings. The footprint extends from the previously implicated plateau to the side of the spike, and into the conserved canyon, covering a larger area than anticipated. Comparison with structures of binding and non-binding serotypes indicates that recognition depends on a combination of subtle serotype-specific features. Separation of the neutralizing epitope from the heparan sulfate cell attachment site encourages attempts to develop immune-resistant vectors that can still bind to target cells. | ||
| - | + | Structure of adeno-associated virus-2 in complex with neutralizing monoclonal antibody A20.,McCraw DM, O'Donnell JK, Taylor KA, Stagg SM, Chapman MS Virology. 2012 Sep 15;431(1-2):40-9. Epub 2012 Jun 9. PMID:22682774<ref>PMID:22682774</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | + | </div> | |
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==See Also== | ==See Also== | ||
| + | *[[Monoclonal Antibody|Monoclonal Antibody]] | ||
*[[Virus coat protein|Virus coat protein]] | *[[Virus coat protein|Virus coat protein]] | ||
| - | + | == References == | |
| - | == | + | <references/> |
| - | < | + | __TOC__ |
| + | </StructureSection> | ||
[[Category: Adeno-associated virus - 2]] | [[Category: Adeno-associated virus - 2]] | ||
[[Category: Mus musculus]] | [[Category: Mus musculus]] | ||
| - | [[Category: Chapman, M S | + | [[Category: Chapman, M S]] |
| - | [[Category: McCraw, D M | + | [[Category: McCraw, D M]] |
[[Category: Epitope]] | [[Category: Epitope]] | ||
[[Category: Fab]] | [[Category: Fab]] | ||
[[Category: Gene therapy]] | [[Category: Gene therapy]] | ||
[[Category: Virus-immune system complex]] | [[Category: Virus-immune system complex]] | ||
Revision as of 08:40, 25 December 2014
Structure of adeno-associated virus-2 in complex with neutralizing monoclonal antibody A20
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