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4liy

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Revision as of 05:30, 5 August 2016

Structure of the adenovirus 3 knob domain K217E and F224S mutant

Structural highlights

4liy is a 3 chain structure. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:
Related:	1h7z
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

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

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/4liy"

@@ Line 1: / Line 1: @@
 ==Structure of the adenovirus 3 knob domain K217E and F224S mutant==
 <StructureSection load='4liy' size='340' side='right' caption='[[4liy]], [[Resolution|resolution]] 2.10&Aring;' scene=''>
@@ Line 5: / Line 6: @@
 </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>
 <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1h7z|1h7z]]</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://www.rcsb.org/pdb/explore.do?structureId=4liy RCSB], [http://www.ebi.ac.uk/pdbsum/4liy PDBsum]</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>
 == Function ==
@@ Line 17: / Line 18: @@
 From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
 </div>
+<div class="pdbe-citations 4liy" style="background-color:#fffaf0;"></div>
 == References ==
 <references/>

4liy

From Proteopedia

Revision as of 05:30, 5 August 2016

Structure of the adenovirus 3 knob domain K217E and F224S mutant

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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