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| | <SX load='3j1s' size='340' side='right' viewer='molstar' caption='[[3j1s]], [[Resolution|resolution]] 8.50Å' scene=''> | | <SX load='3j1s' size='340' side='right' viewer='molstar' caption='[[3j1s]], [[Resolution|resolution]] 8.50Å' scene=''> |
| | == Structural highlights == | | == 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> | + | <table><tr><td colspan='2'>[[3j1s]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus] and [https://en.wikipedia.org/wiki/Adeno-associated_virus_2 Adeno-associated virus 2]. 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 [https://proteopedia.org/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> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 8.5Å</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://pdbe.org/3j1s PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3j1s RCSB], [http://www.ebi.ac.uk/pdbsum/3j1s PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3j1s 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=3j1s FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3j1s OCA], [https://pdbe.org/3j1s PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3j1s RCSB], [https://www.ebi.ac.uk/pdbsum/3j1s PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3j1s ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == 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> | + | [https://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;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | ==See Also== | | ==See Also== |
| | *[[Monoclonal Antibodies 3D structures|Monoclonal Antibodies 3D structures]] | | *[[Monoclonal Antibodies 3D structures|Monoclonal Antibodies 3D structures]] |
| - | *[[Virus coat protein|Virus coat protein]] | + | *[[Virus coat proteins 3D structures|Virus coat proteins 3D structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </SX> | | </SX> |
| - | [[Category: Adeno-associated virus - 2]] | + | [[Category: Adeno-associated virus 2]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| | [[Category: Mus musculus]] | | [[Category: Mus musculus]] |
| - | [[Category: Chapman, M S]] | + | [[Category: Chapman MS]] |
| - | [[Category: McCraw, D M]] | + | [[Category: McCraw DM]] |
| - | [[Category: Epitope]]
| + | |
| - | [[Category: Fab]]
| + | |
| - | [[Category: Gene therapy]]
| + | |
| - | [[Category: Virus-immune system complex]]
| + | |
| Structural highlights
Function
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.[1] [2] [3] [4]
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[5]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Bartlett JS, Wilcher R, Samulski RJ. Infectious entry pathway of adeno-associated virus and adeno-associated virus vectors. J Virol. 2000 Mar;74(6):2777-85. PMID:10684294
- ↑ Girod A, Wobus CE, Zadori Z, Ried M, Leike K, Tijssen P, Kleinschmidt JA, Hallek M. The VP1 capsid protein of adeno-associated virus type 2 is carrying a phospholipase A2 domain required for virus infectivity. J Gen Virol. 2002 May;83(Pt 5):973-8. PMID:11961250
- ↑ Asokan A, Hamra JB, Govindasamy L, Agbandje-McKenna M, Samulski RJ. Adeno-associated virus type 2 contains an integrin alpha5beta1 binding domain essential for viral cell entry. J Virol. 2006 Sep;80(18):8961-9. PMID:16940508 doi:http://dx.doi.org/10.1128/JVI.00843-06
- ↑ Summerford C, Samulski RJ. Membrane-associated heparan sulfate proteoglycan is a receptor for adeno-associated virus type 2 virions. J Virol. 1998 Feb;72(2):1438-45. PMID:9445046
- ↑ McCraw DM, O'Donnell JK, Taylor KA, Stagg SM, Chapman MS. Structure of adeno-associated virus-2 in complex with neutralizing monoclonal antibody A20. Virology. 2012 Sep 15;431(1-2):40-9. Epub 2012 Jun 9. PMID:22682774 doi:10.1016/j.virol.2012.05.004
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