7ltm
From Proteopedia
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==Hum8 capsid== | ==Hum8 capsid== | ||
| - | <StructureSection load='7ltm' size='340' side='right'caption='[[7ltm]]' scene=''> | + | <StructureSection load='7ltm' size='340' side='right'caption='[[7ltm]], [[Resolution|resolution]] 2.49Å' scene=''> |
== Structural highlights == | == Structural highlights == | ||
| - | <table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7LTM OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7LTM FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[7ltm]] is a 60 chain structure with sequence from [https://en.wikipedia.org/wiki/Adeno-associated_virus_-_8 Adeno-associated virus - 8]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7LTM OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7LTM FirstGlance]. <br> |
</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=7ltm FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7ltm OCA], [https://pdbe.org/7ltm PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7ltm RCSB], [https://www.ebi.ac.uk/pdbsum/7ltm PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7ltm ProSAT]</span></td></tr> | </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=7ltm FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7ltm OCA], [https://pdbe.org/7ltm PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7ltm RCSB], [https://www.ebi.ac.uk/pdbsum/7ltm PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7ltm ProSAT]</span></td></tr> | ||
</table> | </table> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | Adeno-associated viruses utilize different glycans and the AAV receptor (AAVR) for cellular attachment and entry. Directed evolution has yielded new AAV variants; however, structure-function correlates underlying their improved transduction are generally overlooked. Here, we report that infectious cycling of structurally diverse AAV surface loop libraries yields functionally distinct variants. Newly evolved variants show enhanced cellular binding, uptake and transduction; but through distinct mechanisms. Using glycan-based and genome-wide CRISPR knockout screens, we discover that one AAV variant acquires the ability to recognize sulfated glycosaminoglycans, while another displays receptor switching from AAVR to Integrin beta1 (ITGB1). A previously evolved variant, AAVhum.8, preferentially utilizes the ITGB1 receptor over AAVR. Visualization of the AAVhum.8 capsid by cryo-EM at 2.49A resolution localizes the newly acquired integrin recognition motif adjacent to the AAVR footprint. These observations underscore the new finding that distinct AAV surface epitopes can be evolved to exploit different cellular receptors for enhanced transduction. Importance Understanding how viruses interact with host cells through cell surface receptors is central to discovery and development of antiviral therapeutics, vaccines and gene transfer vectors. Here, we demonstrate that distinct epitopes on the surface of adeno-associated viruses can be evolved by infectious cycling to recognize different cell surface carbohydrates and glycoprotein receptors and solve the 3D structure of one such newly evolved AAV capsid, which provides a roadmap for designing viruses with improved attributes for gene therapy applications. | ||
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| + | Receptor switching in newly evolved adeno-associated viruses.,Havlik LP, Das A, Mietzsch M, Oh DK, Ark J, McKenna R, Agbandje-McKenna M, Asokan A J Virol. 2021 Jul 7:JVI0058721. doi: 10.1128/JVI.00587-21. PMID:34232726<ref>PMID:34232726</ref> | ||
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| + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| + | </div> | ||
| + | <div class="pdbe-citations 7ltm" style="background-color:#fffaf0;"></div> | ||
| + | == References == | ||
| + | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
| + | [[Category: Adeno-associated virus - 8]] | ||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
| - | [[Category: Agbandje-McKenna M]] | + | [[Category: Agbandje-McKenna, M]] |
| - | [[Category: Mietzsch M]] | + | [[Category: Mietzsch, M]] |
| + | [[Category: Aav8]] | ||
| + | [[Category: Adeno-associated virus]] | ||
| + | [[Category: Capsid engineering]] | ||
| + | [[Category: Gene therapy]] | ||
| + | [[Category: Hum8]] | ||
| + | [[Category: Icosahedral capsid]] | ||
| + | [[Category: Parvovirus]] | ||
| + | [[Category: Virus]] | ||
Revision as of 06:19, 18 August 2021
Hum8 capsid
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