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| | <StructureSection load='6zc5' size='340' side='right'caption='[[6zc5]], [[Resolution|resolution]] 2.50Å' scene=''> | | <StructureSection load='6zc5' size='340' side='right'caption='[[6zc5]], [[Resolution|resolution]] 2.50Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[6zc5]] is a 12 chain structure with sequence from [https://en.wikipedia.org/wiki/Adenovirus_type_10 Adenovirus type 10]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6ZC5 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6ZC5 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[6zc5]] is a 12 chain structure with sequence from [https://en.wikipedia.org/wiki/Human_adenovirus_D10 Human adenovirus D10]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6ZC5 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6ZC5 FirstGlance]. <br> |
| - | </td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[6stt|6stt]]</div></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=6zc5 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6zc5 OCA], [https://pdbe.org/6zc5 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6zc5 RCSB], [https://www.ebi.ac.uk/pdbsum/6zc5 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6zc5 ProSAT]</span></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">L5 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=28275 Adenovirus type 10])</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=6zc5 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6zc5 OCA], [https://pdbe.org/6zc5 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6zc5 RCSB], [https://www.ebi.ac.uk/pdbsum/6zc5 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6zc5 ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| - | <div style="background-color:#fffaf0;">
| + | == Function == |
| - | == Publication Abstract from PubMed == | + | [[https://www.uniprot.org/uniprot/B5BQ05_9ADEN B5BQ05_9ADEN]] |
| - | Oncolytic virotherapies (OV) hold immense clinical potential. OV based on human adenoviruses (HAdV) derived from HAdV with naturally low rates of pre-existing immunity will be beneficial for future clinical translation. We generated a low-seroprevalence HAdV-D10 serotype vector incorporating an alphavbeta6 integrin-selective peptide, A20, to target alphavbeta6-positive tumor cell types. HAdV-D10 has limited natural tropism. Structural and biological studies of HAdV-D10 knob protein highlighted low-affinity engagement with native adenoviral receptors CAR and sialic acid. HAdV-D10 fails to engage blood coagulation factor X, potentially eliminating "off-target" hepatic sequestration in vivo. We engineered an A20 peptide that selectively binds alphavbeta6 integrin into the DG loop of HAdV-D10 fiber knob. Assays in alphavbeta6+ cancer cell lines demonstrated significantly increased transduction mediated by alphavbeta6-targeted variants compared with controls, confirmed microscopically. HAdV-D10.A20 resisted neutralization by neutralizing HAdV-C5 sera. Systemic delivery of HAdV-D10.A20 resulted in significantly increased GFP expression in BT20 tumors. Replication-competent HAdV-D10.A20 demonstrated alphavbeta6 integrin-selective cell killing in vitro and in vivo. HAdV-D10 possesses characteristics of a promising virotherapy, combining low seroprevalence, weak receptor interactions, and reduced off-target uptake. Incorporation of an alphavbeta6 integrin-selective peptide resulted in HAdV-D10.A20, with significant potential for clinical translation.
| + | |
| - | | + | |
| - | Development of a low-seroprevalence, alphavbeta6 integrin-selective virotherapy based on human adenovirus type 10.,Bates EA, Davies JA, Vanova J, Nestic D, Meniel VS, Koushyar S, Cunliffe TG, Mundy RM, Moses E, Uusi-Kerttula HK, Baker AT, Cole DK, Majhen D, Rizkallah PJ, Phesse T, Chester JD, Parker AL Mol Ther Oncolytics. 2022 Mar 16;25:43-56. doi: 10.1016/j.omto.2022.03.007., eCollection 2022 Jun 16. PMID:35399606<ref>PMID:35399606</ref>
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| - | | + | |
| - | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
| + | |
| - | </div>
| + | |
| - | <div class="pdbe-citations 6zc5" style="background-color:#fffaf0;"></div>
| + | |
| - | == References ==
| + | |
| - | <references/>
| + | |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Adenovirus type 10]] | + | [[Category: Human adenovirus D10]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Baker, A T]] | + | [[Category: Baker AT]] |
| - | [[Category: Mundy, R M]] | + | [[Category: Mundy RM]] |
| - | [[Category: Parker, A L]] | + | [[Category: Parker AL]] |
| - | [[Category: Rizkallah, P J]] | + | [[Category: Rizkallah PJ]] |
| - | [[Category: Ad10]]
| + | |
| - | [[Category: Adenoviridae]]
| + | |
| - | [[Category: Adenovirus]]
| + | |
| - | [[Category: Adv]]
| + | |
| - | [[Category: Fiber]]
| + | |
| - | [[Category: Fiber-knob]]
| + | |
| - | [[Category: Fibre]]
| + | |
| - | [[Category: Hadv]]
| + | |
| - | [[Category: Hadv-d10]]
| + | |
| - | [[Category: Head]]
| + | |
| - | [[Category: Knob domain]]
| + | |
| - | [[Category: Piv]]
| + | |
| - | [[Category: Protein iv]]
| + | |
| - | [[Category: Serotype 10]]
| + | |
| - | [[Category: Viral protein]]
| + | |
