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7u96

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Current revision (09:38, 14 February 2024) (edit) (undo)
 
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<StructureSection load='7u96' size='340' side='right'caption='[[7u96]], [[Resolution|resolution]] 2.14&Aring;' scene=''>
<StructureSection load='7u96' size='340' side='right'caption='[[7u96]], [[Resolution|resolution]] 2.14&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
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<table><tr><td colspan='2'>[[7u96]] is a 60 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7U96 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7U96 FirstGlance]. <br>
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<table><tr><td colspan='2'>[[7u96]] is a 60 chain structure with sequence from [https://en.wikipedia.org/wiki/Snake_adeno-associated_virus Snake adeno-associated virus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7U96 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7U96 FirstGlance]. <br>
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</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=7u96 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7u96 OCA], [https://pdbe.org/7u96 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7u96 RCSB], [https://www.ebi.ac.uk/pdbsum/7u96 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7u96 ProSAT]</span></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]] 2.14&#8491;</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=7u96 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7u96 OCA], [https://pdbe.org/7u96 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7u96 RCSB], [https://www.ebi.ac.uk/pdbsum/7u96 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7u96 ProSAT]</span></td></tr>
</table>
</table>
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<div style="background-color:#fffaf0;">
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== Function ==
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== Publication Abstract from PubMed ==
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[https://www.uniprot.org/uniprot/Q6V7U2_9VIRU Q6V7U2_9VIRU]
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Adeno-associated viruses (AAVs) are being developed as clinical gene therapy vectors. One issue undermining their broad use in the clinical setting is the high prevalence of circulating antibodies in the general population capable of neutralizing AAV vectors. Hence, there is a need for AAV vectors that can evade the preexisting immune response. One possible source of human naive vectors are AAVs that do not disseminate in the primate population, and one such example is serpentine AAV (SAAV). This study characterizes the structural and biophysical properties of the SAAV capsid and its receptor interactions and antigenicity. Single particle cryo-electron microscopy (cryo-EM) and thermal stability studies were conducted to characterize the SAAV capsid structure at pH 7.4, 6.0, 5.5, and 4.0, conditions experienced during cellular trafficking. Cell binding assays using Chinese hamster ovary (CHO) cell lines identified terminal sialic acid as the primary attachment receptor for SAAV similar to AAV1, 4, 5, and 6. The binding site of sialic acid to the SAAV capsid was mapped near the 2-fold axis toward the 2/5-fold wall, in a different location than AAV1, 4, 5, and 6. Towards determining the SAAV capsid antigenicity native immunodot blots showed that SAAV evades AAV serotype-specific mouse monoclonal antibodies. However, despite its reptilian origin, it was recognized by ~25% of 50 human sera tested, likely due to the presence of cross-reactive antibodies. These findings will inform future gene delivery applications using SAAV-based vectors and further aid the structural characterization and annotation of the repertoire of available AAV capsids. IMPORTANCE AAVs are widely studied therapeutic gene delivery vectors. However, preexisting antibodies and their detrimental effect on therapeutic efficacy are a primary challenge encountered during clinical trials. In order to circumvent preexisting neutralizing antibodies targeting mammalian AAV capsids, serpentine AAV (SAAV) was evaluated as a potential alternative to existing mammalian therapeutic vectors. The SAAV capsid was found to be thermostable at a wide range of environmental pH conditions, and its structure showed conservation of the core capsid topology but displays high structural variability on the surface. At the same time, it binds to a common receptor, sialic acid, that is also utilized by other AAVs already being utilized in gene therapy trials. Contrary to the initial hypothesis, SAAV capsids were recognized by one in four human sera tested, pointing to conserved amino acids around the 5-fold region as epitopes for cross-reacting antibodies.
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Characterization of the Serpentine Adeno-Associated Virus (SAAV) Capsid Structure: Receptor Interactions and Antigenicity.,Mietzsch M, Hull JA, Makal VE, Jimenez Ybargollin A, Yu JC, McKissock K, Bennett A, Penzes J, Lins-Austin B, Yu Q, Chipman P, Bhattacharya N, Sousa D, Strugatsky D, Tijssen P, McKenna R, Agbandje-McKenna M J Virol. 2022 May 9:e0033522. doi: 10.1128/jvi.00335-22. PMID:35532224<ref>PMID:35532224</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 7u96" style="background-color:#fffaf0;"></div>
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== References ==
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<references/>
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__TOC__
__TOC__
</StructureSection>
</StructureSection>
[[Category: Large Structures]]
[[Category: Large Structures]]
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[[Category: McKenna, R]]
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[[Category: Snake adeno-associated virus]]
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[[Category: Mietzsch, M]]
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[[Category: McKenna R]]
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[[Category: Aav]]
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[[Category: Mietzsch M]]
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[[Category: Capsid]]
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[[Category: Endosomal trafficking]]
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[[Category: Gene therapy]]
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[[Category: Receptor]]
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[[Category: Virus like particle]]
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Current revision

SAAV pH 5.5 capsid structure

PDB ID 7u96

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