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==Adenovirus serotype 10 Fiber-Knob==
==Adenovirus serotype 10 Fiber-Knob==
<StructureSection load='6qpm' size='340' side='right'caption='[[6qpm]]' scene=''>
<StructureSection load='6qpm' size='340' side='right'caption='[[6qpm]], [[Resolution|resolution]] 3.39&Aring;' 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=6QPM OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6QPM FirstGlance]. <br>
<table><tr><td colspan='2'>[[6qpm]] is a 6 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=6QPM OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6QPM FirstGlance]. <br>
</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=6qpm FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6qpm OCA], [http://pdbe.org/6qpm PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6qpm RCSB], [http://www.ebi.ac.uk/pdbsum/6qpm PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6qpm ProSAT]</span></td></tr>
</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=6qpm FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6qpm OCA], [https://pdbe.org/6qpm PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6qpm RCSB], [https://www.ebi.ac.uk/pdbsum/6qpm PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6qpm ProSAT]</span></td></tr>
</table>
</table>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
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>
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 6qpm" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
__TOC__
</StructureSection>
</StructureSection>
[[Category: Adenovirus type 10]]
[[Category: Large Structures]]
[[Category: Large Structures]]
[[Category: Baker AT]]
[[Category: Baker, A T]]
[[Category: Rizkallah PJ]]
[[Category: Rizkallah, P J]]
[[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]]
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