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| <SX load='6e9d' size='340' side='right' viewer='molstar' caption='[[6e9d]], [[Resolution|resolution]] 1.86Å' scene=''> | | <SX load='6e9d' size='340' side='right' viewer='molstar' caption='[[6e9d]], [[Resolution|resolution]] 1.86Å' scene=''> |
| == Structural highlights == | | == Structural highlights == |
| <table><tr><td colspan='2'>[[6e9d]] is a 60 chain structure with sequence from [http://en.wikipedia.org/wiki/Ade02 Ade02]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6E9D OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6E9D FirstGlance]. <br> | | <table><tr><td colspan='2'>[[6e9d]] is a 60 chain structure with sequence from [https://en.wikipedia.org/wiki/Adeno-associated_virus_2_Srivastava/1982 Adeno-associated virus 2 Srivastava/1982]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6E9D OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6E9D FirstGlance]. <br> |
| </td></tr><tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">VP1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10515 ADE02])</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]] 1.86Å</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=6e9d FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6e9d OCA], [http://pdbe.org/6e9d PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6e9d RCSB], [http://www.ebi.ac.uk/pdbsum/6e9d PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6e9d 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=6e9d FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6e9d OCA], [https://pdbe.org/6e9d PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6e9d RCSB], [https://www.ebi.ac.uk/pdbsum/6e9d PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6e9d 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;">
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| == Publication Abstract from PubMed ==
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| Single-particle cryogenic electron microscopy (cryo-EM) provides a powerful methodology for structural biologists, but the resolutions typically attained with experimentally determined structures have lagged behind microscope capabilities. Here, we exploit several technical advances to improve resolution, including per-particle contrast transfer function (CTF) refinement and correction for Ewald sphere curvature. The latter is demonstrated with several experimental samples and should become more standard as resolutions increase or at lower microscope accelerating voltages. The combined application of the described methods to micrographs recorded on a Titan Krios enables structure determination at ~1.86-A resolution of an adeno-associated virus serotype 2 variant (AAV2), an important gene-delivery vehicle. The resulting structural details provide an improved model for understanding the biology of AAV that will guide future vector development for gene therapy.
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| Sub-2 A Ewald curvature corrected structure of an AAV2 capsid variant.,Tan YZ, Aiyer S, Mietzsch M, Hull JA, McKenna R, Grieger J, Samulski RJ, Baker TS, Agbandje-McKenna M, Lyumkis D Nat Commun. 2018 Sep 7;9(1):3628. doi: 10.1038/s41467-018-06076-6. PMID:30194371<ref>PMID:30194371</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>
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| <div class="pdbe-citations 6e9d" style="background-color:#fffaf0;"></div>
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| == References == | | == References == |
| <references/> | | <references/> |
| __TOC__ | | __TOC__ |
| </SX> | | </SX> |
| [[Category: Ade02]] | | [[Category: Adeno-associated virus 2 Srivastava/1982]] |
| [[Category: Large Structures]] | | [[Category: Large Structures]] |
| [[Category: Agbandje-McKenna, M]] | | [[Category: Agbandje-McKenna M]] |
| [[Category: Aiyer, S]] | | [[Category: Aiyer S]] |
| [[Category: Baker, T S]] | | [[Category: Baker TS]] |
| [[Category: Hull, J A]] | | [[Category: Hull JA]] |
| [[Category: Lyumkis, D]] | | [[Category: Lyumkis D]] |
| [[Category: McKenna, R]] | | [[Category: McKenna R]] |
| [[Category: Mietzsch, M]] | | [[Category: Mietzsch M]] |
| [[Category: Tan, Y Z]] | | [[Category: Tan YZ]] |
| [[Category: Aav-2 l336c]]
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| [[Category: Ewald sphere curvature correction]]
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| [[Category: Gene therapy]]
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| [[Category: Per particle ctf]]
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| [[Category: Virus like particle]]
| |