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| | == Structural highlights == | | == Structural highlights == |
| | <table><tr><td colspan='2'>[[3j4p]] 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=3J4P OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3J4P FirstGlance]. <br> | | <table><tr><td colspan='2'>[[3j4p]] 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=3J4P OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3J4P FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=GU4:2,3,4,6-TETRA-O-SULFONATO-ALPHA-D-GLUCOPYRANOSE'>GU4</scene></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]] 4.8Å</td></tr> |
| - | <tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=YYJ:'>YYJ</scene></td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GU4:2,3,4,6-TETRA-O-SULFONATO-ALPHA-D-GLUCOPYRANOSE'>GU4</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=PRD_900013:sucrose+octasulfate'>PRD_900013</scene>, <scene name='pdbligand=YYJ:1,3,4,6-tetra-O-sulfo-beta-D-fructofuranose'>YYJ</scene></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">cap ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=272636 Adeno-associated virus])</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=3j4p FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3j4p OCA], [https://pdbe.org/3j4p PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3j4p RCSB], [https://www.ebi.ac.uk/pdbsum/3j4p PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3j4p 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=3j4p FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3j4p OCA], [https://pdbe.org/3j4p PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3j4p RCSB], [https://www.ebi.ac.uk/pdbsum/3j4p PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3j4p ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | + | == Function == |
| | + | [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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| | [[Category: Adeno-associated virus]] | | [[Category: Adeno-associated virus]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Chapman, M S]] | + | [[Category: Chapman MS]] |
| - | [[Category: Xie, Q]] | + | [[Category: Xie Q]] |
| - | [[Category: Virus]]
| + | |
| - | [[Category: Virus cell-receptor interaction]]
| + | |
| 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
Mechanistic studies of macromolecular complexes often feature X-ray structures of complexes with bound ligands. The attachment of adeno-associated virus (AAV) to cell surface glycosaminoglycans (GAGs) is an example that has not proven amenable to crystallography, because the binding of GAG analogs disrupts lattice contacts. The interactions of AAV with GAGs are of interest in mediating the cell specificity of AAV-based gene therapy vectors. Previous electron microscopy led to differing conclusions on the exact binding site and the existence of large ligand-induced conformational changes in the virus. Conformational changes are expected during cell entry, but it has remained unclear whether the electron microscopy provided evidence of their induction by GAG-binding. Taking advantage of automated data collection, careful processing and new methods of structure refinement, the structure of AAV-DJ complexed with sucrose octasulfate is determined by electron microscopy difference map analysis to 4.8A resolution. At this higher resolution, individual sulfate groups are discernible, providing a stereochemical validation of map interpretation, and highlighting interactions with two surface arginines that have been implicated in genetic studies. Conformational changes induced by the SOS are modest and limited to the loop most directly interacting with the ligand. While the resolution attainable will depend on sample order and other factors, there are an increasing number of macromolecular complexes that can be studied by cryo-electron microscopy at resolutions beyond 5A, for which the approaches used here could be used to characterize the binding of inhibitors and other small molecule effectors when crystallography is not tractable.
Electron microscopy analysis of a disaccharide analog complex reveals receptor interactions of adeno-associated virus.,Xie Q, Spilman M, Meyer NL, Lerch TF, Stagg SM, Chapman MS J Struct Biol. 2013 Sep 11. pii: S1047-8477(13)00234-7. doi:, 10.1016/j.jsb.2013.09.004. PMID:24036405[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, Spilman M, Meyer NL, Lerch TF, Stagg SM, Chapman MS. Electron microscopy analysis of a disaccharide analog complex reveals receptor interactions of adeno-associated virus. J Struct Biol. 2013 Sep 11. pii: S1047-8477(13)00234-7. doi:, 10.1016/j.jsb.2013.09.004. PMID:24036405 doi:http://dx.doi.org/10.1016/j.jsb.2013.09.004
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