6nz0

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==Cryo-EM structure of AAV-2 in complex with AAVR PKD domains 1 and 2==
==Cryo-EM structure of AAV-2 in complex with AAVR PKD domains 1 and 2==
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<StructureSection load='6nz0' size='340' side='right'caption='[[6nz0]], [[Resolution|resolution]] 2.40&Aring;' scene=''>
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<SX load='6nz0' size='340' side='right' viewer='molstar' caption='[[6nz0]], [[Resolution|resolution]] 2.40&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
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<table><tr><td colspan='2'>[[6nz0]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6NZ0 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6NZ0 FirstGlance]. <br>
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<table><tr><td colspan='2'>[[6nz0]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Adeno-associated_virus_2_Srivastava/1982 Adeno-associated virus 2 Srivastava/1982] and [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6NZ0 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6NZ0 FirstGlance]. <br>
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</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene></td></tr>
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 2.4&#8491;</td></tr>
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<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=6nz0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6nz0 OCA], [http://pdbe.org/6nz0 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6nz0 RCSB], [http://www.ebi.ac.uk/pdbsum/6nz0 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6nz0 ProSAT]</span></td></tr>
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<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene></td></tr>
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=6nz0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6nz0 OCA], [https://pdbe.org/6nz0 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6nz0 RCSB], [https://www.ebi.ac.uk/pdbsum/6nz0 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6nz0 ProSAT]</span></td></tr>
</table>
</table>
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== Disease ==
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<div style="background-color:#fffaf0;">
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[[http://www.uniprot.org/uniprot/K319L_HUMAN K319L_HUMAN]] Systemic lupus erythematosus;Limited cutaneous systemic sclerosis.
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== Publication Abstract from PubMed ==
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== Function ==
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Adeno-associated virus (AAV) vectors are preeminent in emerging clinical gene therapies. Generalizing beyond the most tractable genetic diseases will require modulation of cell specificity and immune neutralization. Interactions of AAV with its cellular receptor, AAVR, are key to understanding cell-entry and trafficking with the rigor needed to engineer tissue-specific vectors. Cryo-electron tomography shows ordered binding of part of the flexible receptor to the viral surface, with distal domains in multiple conformations. Regions of the virus and receptor in close physical proximity can be identified by cross-linking/mass spectrometry. Cryo-electron microscopy with a two-domain receptor fragment reveals the interactions at 2.4 A resolution. AAVR binds between AAV's spikes on a plateau that is conserved, except in one clade whose structure is AAVR-incompatible. AAVR's footprint overlaps the epitopes of several neutralizing antibodies, prompting a re-evaluation of neutralization mechanisms. The structure provides a roadmap for experimental probing and manipulation of viral-receptor interactions.
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[[http://www.uniprot.org/uniprot/K319L_HUMAN K319L_HUMAN]] Possible role in axon guidance through interaction with RTN4R.<ref>PMID:20697954</ref> [[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>
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Structure of the gene therapy vector, adeno-associated virus with its cell receptor, AAVR.,Meyer NL, Hu G, Davulcu O, Xie Q, Noble AJ, Yoshioka C, Gingerich DS, Trzynka A, David L, Stagg SM, Chapman MS Elife. 2019 May 22;8. pii: 44707. doi: 10.7554/eLife.44707. PMID:31115336<ref>PMID:31115336</ref>
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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</div>
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<div class="pdbe-citations 6nz0" style="background-color:#fffaf0;"></div>
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==See Also==
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*[[Virus coat proteins 3D structures|Virus coat proteins 3D structures]]
== References ==
== References ==
<references/>
<references/>
__TOC__
__TOC__
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</StructureSection>
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</SX>
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[[Category: Adeno-associated virus 2 Srivastava/1982]]
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[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Large Structures]]
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[[Category: Chapman, M S]]
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[[Category: Chapman MS]]
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[[Category: Davulcu, O]]
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[[Category: Davulcu O]]
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[[Category: Meyer, N L]]
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[[Category: Meyer NL]]
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[[Category: Xie, Q]]
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[[Category: Xie Q]]
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[[Category: Yoshioka, C]]
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[[Category: Yoshioka C]]
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[[Category: Aav]]
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[[Category: Aavr]]
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[[Category: Coreceptor]]
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[[Category: Kiaa0319l]]
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[[Category: Parvovirus]]
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[[Category: Pkd]]
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[[Category: Receptor]]
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[[Category: Virus]]
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Current revision

Cryo-EM structure of AAV-2 in complex with AAVR PKD domains 1 and 2

6nz0, resolution 2.40Å

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