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| | <StructureSection load='4lu5' size='340' side='right'caption='[[4lu5]], [[Resolution|resolution]] 2.90Å' scene=''> | | <StructureSection load='4lu5' size='340' side='right'caption='[[4lu5]], [[Resolution|resolution]] 2.90Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4lu5]] is a 6 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=4LU5 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4LU5 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4lu5]] is a 6 chain structure with sequence from [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus] 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=4LU5 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4LU5 FirstGlance]. <br> |
| - | </td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4lqf|4lqf]], [[4m1g|4m1g]]</td></tr> | + | </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=4lu5 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4lu5 OCA], [https://pdbe.org/4lu5 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4lu5 RCSB], [https://www.ebi.ac.uk/pdbsum/4lu5 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4lu5 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=4lu5 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4lu5 OCA], [http://pdbe.org/4lu5 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4lu5 RCSB], [http://www.ebi.ac.uk/pdbsum/4lu5 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4lu5 ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | + | == Function == |
| | + | [https://www.uniprot.org/uniprot/Q71TT1_9POXV Q71TT1_9POXV] |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | </StructureSection> | | </StructureSection> |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Lk3 transgenic mice]] | + | [[Category: Mus musculus]] |
| | [[Category: Vaccinia virus]] | | [[Category: Vaccinia virus]] |
| - | [[Category: Matho, M H]] | + | [[Category: Matho MH]] |
| - | [[Category: Schlossman, A M]] | + | [[Category: Schlossman AM]] |
| - | [[Category: Zajonc, D M]] | + | [[Category: Zajonc DM]] |
| - | [[Category: A33r antigen]]
| + | |
| - | [[Category: Antibody-antigen complex]]
| + | |
| - | [[Category: Ch1]]
| + | |
| - | [[Category: Fv]]
| + | |
| - | [[Category: Igg domain]]
| + | |
| - | [[Category: Igg2a]]
| + | |
| - | [[Category: Immune system]]
| + | |
| - | [[Category: Papain digest of the mab]]
| + | |
| Structural highlights
Function
Q71TT1_9POXV
Publication Abstract from PubMed
Vaccinia virus A33 is an extracellular enveloped virus (EEV)-specific type II membrane glycoprotein that is essential for efficient EEV formation and long-range viral spread within the host. A33 is a target for neutralizing antibody responses against EEV. In this study, we produced seven murine anti-A33 monoclonal antibodies (MAbs) by immunizing mice with live VACV, followed by boosting with the soluble A33 homodimeric ectodomain. Five A33 specific MAbs were capable of neutralizing EEV in the presence of complement. All MAbs bind to conformational epitopes on A33 but not to linear peptides. To identify the epitopes, we have adetermined the crystal structures of three representative neutralizing MAbs in complex with A33. We have further determined the binding kinetics for each of the three antibodies to wild-type A33, as well as to engineered A33 that contained single alanine substitutions within the epitopes of the three crystallized antibodies. While the Fab of both MAbs A2C7 and A20G2 binds to a single A33 subunit, the Fab from MAb A27D7 binds to both A33 subunits simultaneously. A27D7 binding is resistant to single alanine substitutions within the A33 epitope. A27D7 also demonstrated high-affinity binding with recombinant A33 protein that mimics other orthopoxvirus strains in the A27D7 epitope, such as ectromelia, monkeypox, and cowpox virus, suggesting that A27D7 is a potent cross-neutralizer. Finally, we confirmed that A27D7 protects mice against a lethal challenge with ectromelia virus.
Structural and Functional Characterization of Anti-A33 Antibodies Reveal a Potent Cross-Species Orthopoxviruses Neutralizer.,Matho MH, Schlossman A, Meng X, Benhnia MR, Kaever T, Buller M, Doronin K, Parker S, Peters B, Crotty S, Xiang Y, Zajonc DM PLoS Pathog. 2015 Sep 1;11(9):e1005148. doi: 10.1371/journal.ppat.1005148., eCollection 2015 Sep. PMID:26325270[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Matho MH, Schlossman A, Meng X, Benhnia MR, Kaever T, Buller M, Doronin K, Parker S, Peters B, Crotty S, Xiang Y, Zajonc DM. Structural and Functional Characterization of Anti-A33 Antibodies Reveal a Potent Cross-Species Orthopoxviruses Neutralizer. PLoS Pathog. 2015 Sep 1;11(9):e1005148. doi: 10.1371/journal.ppat.1005148., eCollection 2015 Sep. PMID:26325270 doi:http://dx.doi.org/10.1371/journal.ppat.1005148
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