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| | <StructureSection load='1lp3' size='340' side='right'caption='[[1lp3]], [[Resolution|resolution]] 3.00Å' scene=''> | | <StructureSection load='1lp3' size='340' side='right'caption='[[1lp3]], [[Resolution|resolution]] 3.00Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[1lp3]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Aav-2 Aav-2]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1LP3 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1LP3 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[1lp3]] is a 1 chain structure with sequence from [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=1LP3 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1LP3 FirstGlance]. <br> |
| - | </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=1lp3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1lp3 OCA], [http://pdbe.org/1lp3 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1lp3 RCSB], [http://www.ebi.ac.uk/pdbsum/1lp3 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=1lp3 ProSAT]</span></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]] 3Å</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=1lp3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1lp3 OCA], [https://pdbe.org/1lp3 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1lp3 RCSB], [https://www.ebi.ac.uk/pdbsum/1lp3 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1lp3 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> |
| | == Evolutionary Conservation == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
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| | ==See Also== | | ==See Also== |
| - | *[[Virus coat protein|Virus coat protein]] | + | *[[Virus coat proteins 3D structures|Virus coat proteins 3D structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Aav-2]] | + | [[Category: Adeno-associated virus 2]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Azzi, A]] | + | [[Category: Azzi A]] |
| - | [[Category: Bhatia, S]] | + | [[Category: Bhatia S]] |
| - | [[Category: Bu, W]] | + | [[Category: Bu W]] |
| - | [[Category: Chapman, M S]] | + | [[Category: Chapman MS]] |
| - | [[Category: Hare, J]] | + | [[Category: Hare J]] |
| - | [[Category: Somasundaram, T]] | + | [[Category: Somasundaram T]] |
| - | [[Category: Xie, Q]] | + | [[Category: Xie Q]] |
| - | [[Category: Beta-barrel]]
| + | |
| - | [[Category: Capsid]]
| + | |
| - | [[Category: Dna]]
| + | |
| - | [[Category: Human]]
| + | |
| - | [[Category: Icosahedral virus]]
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| - | [[Category: Parvovirus]]
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| - | [[Category: Satellite]]
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| - | [[Category: Single-stranded]]
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| - | [[Category: Virus]]
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| 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]
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
The structure of the adeno-associated virus (AAV-2) has been determined to 3-A resolution by x-ray crystallography. AAV is being developed as a vector for gene therapy to treat diseases including hemophilia, cancer, and cystic fibrosis. As in the distantly related autonomous parvoviruses, the capsid protein has a beta-barrel fold, but long loops between the beta-strands share little structural homology with other parvoviruses, leading to unique surface features. Most prominent are groups of threefold-related peaks, each an intimate association of loops from two neighboring subunits. Mutations affecting cell entry and receptor binding are clustered near the positively charged side of each peak, implicating the region in attachment to the cellular receptor, heparan sulfate proteoglycan. Amino acids involved in antibody binding are in the same general vicinity. The structure will guide rational engineering of vector capsids to tailor cellular targeting and to avoid immediate neutralization by an immune system sensitized by prior exposure to AAV.
The atomic structure of adeno-associated virus (AAV-2), a vector for human gene therapy.,Xie Q, Bu W, Bhatia S, Hare J, Somasundaram T, Azzi A, Chapman MS Proc Natl Acad Sci U S A. 2002 Aug 6;99(16):10405-10. Epub 2002 Jul 22. PMID:12136130[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
- ↑ Xie Q, Bu W, Bhatia S, Hare J, Somasundaram T, Azzi A, Chapman MS. The atomic structure of adeno-associated virus (AAV-2), a vector for human gene therapy. Proc Natl Acad Sci U S A. 2002 Aug 6;99(16):10405-10. Epub 2002 Jul 22. PMID:12136130 doi:http://dx.doi.org/10.1073/pnas.162250899
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