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| | ==Three dimensional structure of broadly neutralizing anti - Hepatitis C virus (HCV) glycoprotein E2 alpaca nanobody D03== | | ==Three dimensional structure of broadly neutralizing anti - Hepatitis C virus (HCV) glycoprotein E2 alpaca nanobody D03== |
| - | <StructureSection load='4jvp' size='340' side='right' caption='[[4jvp]], [[Resolution|resolution]] 1.76Å' scene=''> | + | <StructureSection load='4jvp' size='340' side='right'caption='[[4jvp]], [[Resolution|resolution]] 1.76Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4jvp]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Vicugna_pacos Vicugna pacos]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4JVP OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4JVP FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4jvp]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Vicugna_pacos Vicugna pacos]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4JVP OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4JVP 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]] 1.76Å</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=4jvp FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4jvp OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4jvp RCSB], [http://www.ebi.ac.uk/pdbsum/4jvp PDBsum]</span></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='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=4jvp FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4jvp OCA], [https://pdbe.org/4jvp PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4jvp RCSB], [https://www.ebi.ac.uk/pdbsum/4jvp PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4jvp ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
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| | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> |
| | </div> | | </div> |
| | + | <div class="pdbe-citations 4jvp" style="background-color:#fffaf0;"></div> |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| | + | [[Category: Large Structures]] |
| | [[Category: Vicugna pacos]] | | [[Category: Vicugna pacos]] |
| - | [[Category: Krey, T]] | + | [[Category: Krey T]] |
| - | [[Category: Rey, F A]] | + | [[Category: Rey FA]] |
| - | [[Category: Antibody]]
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| - | [[Category: Heavy-chain antibody]]
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| - | [[Category: Immune system]]
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| - | [[Category: Immunoglobulin fold]]
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| - | [[Category: Nanobody]]
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| Structural highlights
Publication Abstract from PubMed
Severe liver disease caused by chronic hepatitis C virus is the major indication for liver transplantation. Despite recent advances in antiviral therapy, drug toxicity and unwanted side-effects render effective treatment in liver-transplanted patients a challenging task. Virus-specific therapeutic antibodies are generally safe and well-tolerated, but their potential in preventing and treating HCV infection has not yet been realized due to a variety of issues, not least high production costs and virus variability. Heavy-chain antibodies (HCAbs) or nanobodies, produced by camelids, represent an exciting antiviral approach - they can target novel highly conserved epitopes that are inaccessible to normal antibodies and they are also easy to manipulate and produce. We isolated four distinct nanobodies from a phage-display library generated from an alpaca immunized with Hepatitis C virus E2 glycoprotein. One of them, nanobody D03, recognized a novel epitope overlapping with the epitopes of several broadly neutralizing human monoclonal antibodies. Its crystal structure revealed a long CDR3 folding over part of the framework that - in conventional antibodies - forms the interface between heavy and light chain. D03 neutralized a panel of retroviral particles pseudotyped with HCV glycoproteins from six genotypes and authentic cell-culture derived particles by interfering with E2-CD81 interaction. In contrast to some of the most broadly neutralizing human anti-E2 mAbs, D03 efficiently inhibited HCV cell-to-cell transmission. Conclusion:This is the first description of a potent and broadly neutralizing HCV-specific nanobody representing a significant advance that will lead to future development of novel entry inhibitors for the treatment and prevention of HCV infection and help our understanding of HCV cell-to-cell transmission. (HEPATOLOGY 2013.).
An alpaca nanobody inhibits hepatitis C virus entry and cell-to-cell transmission.,Tarr AW, Lafaye P, Meredith L, Damier-Piolle L, Urbanowicz RA, Meola A, Jestin JL, Brown RJ, McKeating JA, Rey FA, Ball JK, Krey T Hepatology. 2013 Mar 28. doi: 10.1002/hep.26430. PMID:23553604[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Tarr AW, Lafaye P, Meredith L, Damier-Piolle L, Urbanowicz RA, Meola A, Jestin JL, Brown RJ, McKeating JA, Rey FA, Ball JK, Krey T. An alpaca nanobody inhibits hepatitis C virus entry and cell-to-cell transmission. Hepatology. 2013 Mar 28. doi: 10.1002/hep.26430. PMID:23553604 doi:http://dx.doi.org/10.1002/hep.26430
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