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| | <StructureSection load='4liy' size='340' side='right'caption='[[4liy]], [[Resolution|resolution]] 2.10Å' scene=''> | | <StructureSection load='4liy' size='340' side='right'caption='[[4liy]], [[Resolution|resolution]] 2.10Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4liy]] is a 3 chain structure with sequence from [http://en.wikipedia.org/wiki/Ade03 Ade03]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4LIY OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4LIY FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4liy]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Human_adenovirus_B3 Human adenovirus B3]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4LIY OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4LIY FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.1Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1h7z|1h7z]]</td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">L5 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=45659 ADE03])</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=4liy FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4liy OCA], [https://pdbe.org/4liy PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4liy RCSB], [https://www.ebi.ac.uk/pdbsum/4liy PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4liy ProSAT]</span></td></tr> |
| - | <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=4liy FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4liy OCA], [http://pdbe.org/4liy PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4liy RCSB], [http://www.ebi.ac.uk/pdbsum/4liy PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4liy ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/SPIKE_ADE03 SPIKE_ADE03]] Forms spikes that protrude from each vertex of the icosahedral capsid. Interacts with host receptor CD46 to provide virion initial attachment to target cell. Fiber proteins are shed during virus entry, when virus is still at the cell surface. Heparan sulfate might also play a role in virus binding. | + | [https://www.uniprot.org/uniprot/SPIKE_ADE03 SPIKE_ADE03] Forms spikes that protrude from each vertex of the icosahedral capsid. Interacts with host receptor CD46 to provide virion initial attachment to target cell. Fiber proteins are shed during virus entry, when virus is still at the cell surface. Heparan sulfate might also play a role in virus binding. |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Ade03]] | + | [[Category: Human adenovirus B3]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Fender, P]] | + | [[Category: Fender P]] |
| - | [[Category: Zubieta, C]] | + | [[Category: Zubieta C]] |
| - | [[Category: Adenovirus fibre protein knob domain]]
| + | |
| - | [[Category: Desmoglein 2]]
| + | |
| - | [[Category: Receptor interaction]]
| + | |
| - | [[Category: Viral attachment to host cell]]
| + | |
| - | [[Category: Viral protein]]
| + | |
| Structural highlights
Function
SPIKE_ADE03 Forms spikes that protrude from each vertex of the icosahedral capsid. Interacts with host receptor CD46 to provide virion initial attachment to target cell. Fiber proteins are shed during virus entry, when virus is still at the cell surface. Heparan sulfate might also play a role in virus binding.
Publication Abstract from PubMed
Human adenovirus (Ad) serotypes Ad3, Ad7, Ad11, and Ad14, as well as a recently emerged strain of Ad14 (Ad14p1), use the epithelial junction protein desmoglein 2 (DSG2) as a receptor for infection. Unlike Ad interaction with CAR and CD46, structural details for Ad binding to DSG2 are still elusive. Using an approach based on Escherichia coli expression libraries of random Ad3 and Ad14p1 fiber knob mutants, we identified amino acid residues that, when mutated individually, ablated or reduced Ad knob binding to DSG2. These residues formed three clusters inside one groove at the extreme distal end of the fiber knob. The Ad3 fiber knob mutant library was also used to identify variants with increased affinity to DSG2. We found a number of mutations within or near the EF loop of the Ad3 knob that resulted in affinities to DSG2 that were several orders of magnitude higher than those to the wild-type Ad3 knob. Crystal structure analysis of one of the mutants showed that the introduced mutations make the EF loop more flexible, which might facilitate the interaction with DSG2. Our findings have practical relevance for cancer therapy. We have recently reported that an Ad3 fiber knob-containing recombinant protein (JO-1) is able to trigger opening of junctions between epithelial cancer cells which, in turn, greatly improved the intratumoral penetration and efficacy of therapeutic agents (I. Beyer, et al., Clin. Cancer Res. 18:3340-3351, 2012; I. Beyer, et al., Cancer Res. 71:7080-7090, 2011). Here, we show that affinity-enhanced versions of JO-1 are therapeutically more potent than the parental protein in a series of cancer models.
Structural and functional studies on the interaction of adenovirus fiber knobs and desmoglein 2.,Wang H, Yumul R, Cao H, Ran L, Fan X, Richter M, Epstein F, Gralow J, Zubieta C, Fender P, Lieber A J Virol. 2013 Nov;87(21):11346-62. doi: 10.1128/JVI.01825-13. Epub 2013 Aug 14. PMID:23946456[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Wang H, Yumul R, Cao H, Ran L, Fan X, Richter M, Epstein F, Gralow J, Zubieta C, Fender P, Lieber A. Structural and functional studies on the interaction of adenovirus fiber knobs and desmoglein 2. J Virol. 2013 Nov;87(21):11346-62. doi: 10.1128/JVI.01825-13. Epub 2013 Aug 14. PMID:23946456 doi:http://dx.doi.org/10.1128/JVI.01825-13
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