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| | ==Structure of Fab 7D11 from a neutralizing antibody against the poxvirus L1 protein== | | ==Structure of Fab 7D11 from a neutralizing antibody against the poxvirus L1 protein== |
| - | <StructureSection load='2i9l' size='340' side='right' caption='[[2i9l]], [[Resolution|resolution]] 3.10Å' scene=''> | + | <StructureSection load='2i9l' size='340' side='right'caption='[[2i9l]], [[Resolution|resolution]] 3.10Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[2i9l]] is a 12 chain structure with sequence from [http://en.wikipedia.org/wiki/Lk3_transgenic_mice Lk3 transgenic mice] and [http://en.wikipedia.org/wiki/Vaccinia_virus Vaccinia virus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2I9L OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2I9L FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[2i9l]] is a 12 chain structure with sequence from [https://en.wikipedia.org/wiki/Lk3_transgenic_mice Lk3 transgenic mice] and [https://en.wikipedia.org/wiki/Vaccinia_virus Vaccinia virus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2I9L OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2I9L FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene></td></tr> | + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">l1r ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10245 Vaccinia virus])</td></tr> | + | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">l1r ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10245 Vaccinia virus])</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=2i9l FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2i9l OCA], [http://pdbe.org/2i9l PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2i9l RCSB], [http://www.ebi.ac.uk/pdbsum/2i9l PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2i9l ProSAT]</span></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=2i9l FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2i9l OCA], [https://pdbe.org/2i9l PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2i9l RCSB], [https://www.ebi.ac.uk/pdbsum/2i9l PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2i9l ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/L1_VACCW L1_VACCW]] Envelope protein which probably plays a role in virus entry into the host cell. Is probably involved in the virus attachment to the host cell surface and associates with the entry/fusion complex (EFC). Needed for fusion and penetration of the virus core into host cell.<ref>PMID:8083978</ref> <ref>PMID:18596103</ref> <ref>PMID:19162289</ref> | + | [[https://www.uniprot.org/uniprot/L1_VACCW L1_VACCW]] Envelope protein which probably plays a role in virus entry into the host cell. Is probably involved in the virus attachment to the host cell surface and associates with the entry/fusion complex (EFC). Needed for fusion and penetration of the virus core into host cell.<ref>PMID:8083978</ref> <ref>PMID:18596103</ref> <ref>PMID:19162289</ref> |
| | == Evolutionary Conservation == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
| | Check<jmol> | | Check<jmol> |
| | <jmolCheckbox> | | <jmolCheckbox> |
| - | <scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/i9/2i9l_consurf.spt"</scriptWhenChecked> | + | <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/i9/2i9l_consurf.spt"</scriptWhenChecked> |
| | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> | | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> |
| | <text>to colour the structure by Evolutionary Conservation</text> | | <text>to colour the structure by Evolutionary Conservation</text> |
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| | ==See Also== | | ==See Also== |
| - | *[[3D structures of monoclonal antibody|3D structures of monoclonal antibody]] | + | *[[Monoclonal Antibodies 3D structures|Monoclonal Antibodies 3D structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| | + | [[Category: Large Structures]] |
| | [[Category: Lk3 transgenic mice]] | | [[Category: Lk3 transgenic mice]] |
| | [[Category: Vaccinia virus]] | | [[Category: Vaccinia virus]] |
| Structural highlights
Function
[L1_VACCW] Envelope protein which probably plays a role in virus entry into the host cell. Is probably involved in the virus attachment to the host cell surface and associates with the entry/fusion complex (EFC). Needed for fusion and penetration of the virus core into host cell.[1] [2] [3]
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
Medical countermeasures to prevent or treat smallpox are needed due to the potential use of poxviruses as biological weapons. Safety concerns with the currently available smallpox vaccine indicate a need for research on alternative poxvirus vaccine strategies. Molecular vaccines involving the use of proteins and/or genes and recombinant antibodies are among the strategies under current investigation. The poxvirus L1 protein, encoded by the L1R open reading frame, is the target of neutralizing antibodies and has been successfully used as a component of both protein subunit and DNA vaccines. L1-specific monoclonal antibodies (e.g., mouse monoclonal antibody mAb-7D11, mAb-10F5) with potent neutralizing activity bind L1 in a conformation-specific manner. This suggests that proper folding of the L1 protein used in molecular vaccines will affect the production of neutralizing antibodies and protection. Here, we co-crystallized the Fab fragment of mAb-7D11 with the L1 protein. The crystal structure of the complex between Fab-7D11 and L1 reveals the basis for the conformation-specific binding as recognition of a discontinuous epitope containing two loops that are held together by a disulfide bond. The structure of this important conformational epitope of L1 will contribute to the development of molecular poxvirus vaccines and also provides a novel target for anti-poxvirus drugs. In addition, the sequence and structure of Fab-7D11 will contribute to the development of L1-targeted immunotherapeutics.
Structural basis for the binding of the neutralizing antibody, 7D11, to the poxvirus L1 protein.,Su HP, Golden JW, Gittis AG, Hooper JW, Garboczi DN Virology. 2007 Nov 25;368(2):331-41. Epub 2007 Aug 3. PMID:17688903[4]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Ravanello MP, Hruby DE. Conditional lethal expression of the vaccinia virus L1R myristylated protein reveals a role in virion assembly. J Virol. 1994 Oct;68(10):6401-10. PMID:8083978
- ↑ Bisht H, Weisberg AS, Moss B. Vaccinia virus l1 protein is required for cell entry and membrane fusion. J Virol. 2008 Sep;82(17):8687-94. doi: 10.1128/JVI.00852-08. Epub 2008 Jul 2. PMID:18596103 doi:http://dx.doi.org/10.1128/JVI.00852-08
- ↑ Foo CH, Lou H, Whitbeck JC, Ponce-de-Leon M, Atanasiu D, Eisenberg RJ, Cohen GH. Vaccinia virus L1 binds to cell surfaces and blocks virus entry independently of glycosaminoglycans. Virology. 2009 Mar 15;385(2):368-82. doi: 10.1016/j.virol.2008.12.019. Epub 2009 , Jan 21. PMID:19162289 doi:http://dx.doi.org/10.1016/j.virol.2008.12.019
- ↑ Su HP, Golden JW, Gittis AG, Hooper JW, Garboczi DN. Structural basis for the binding of the neutralizing antibody, 7D11, to the poxvirus L1 protein. Virology. 2007 Nov 25;368(2):331-41. Epub 2007 Aug 3. PMID:17688903 doi:10.1016/j.virol.2007.06.042
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