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| | ==Crystal structure of the anti-AaHI Fab9C2 antibody== | | ==Crystal structure of the anti-AaHI Fab9C2 antibody== |
| - | <StructureSection load='4aeh' size='340' side='right' caption='[[4aeh]], [[Resolution|resolution]] 1.60Å' scene=''> | + | <StructureSection load='4aeh' size='340' side='right'caption='[[4aeh]], [[Resolution|resolution]] 1.60Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4aeh]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4AEH OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4AEH FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4aeh]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4AEH OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4AEH FirstGlance]. <br> |
| - | </td></tr><tr><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4aeh FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4aeh OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4aeh RCSB], [http://www.ebi.ac.uk/pdbsum/4aeh PDBsum]</span></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]] 1.6Å</td></tr> |
| - | <table> | + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=4aeh FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4aeh OCA], [https://pdbe.org/4aeh PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4aeh RCSB], [https://www.ebi.ac.uk/pdbsum/4aeh PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4aeh ProSAT]</span></td></tr> |
| | + | </table> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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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 4aeh" style="background-color:#fffaf0;"></div> |
| | | | |
| | ==See Also== | | ==See Also== |
| - | *[[Monoclonal Antibody|Monoclonal Antibody]] | + | *[[Monoclonal Antibodies 3D structures|Monoclonal Antibodies 3D structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| | + | [[Category: Large Structures]] |
| | [[Category: Mus musculus]] | | [[Category: Mus musculus]] |
| - | [[Category: Bourne, Y.]] | + | [[Category: Bourne Y]] |
| - | [[Category: Conrod, S.]] | + | [[Category: Conrod S]] |
| - | [[Category: Fabrichny, I P.]] | + | [[Category: Fabrichny IP]] |
| - | [[Category: Marchot, P.]] | + | [[Category: Marchot P]] |
| - | [[Category: Martin-Eauclaire, M F.]] | + | [[Category: Martin-Eauclaire MF]] |
| - | [[Category: Mondielli, G.]] | + | [[Category: Mondielli G]] |
| - | [[Category: Alpha-toxin]]
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| - | [[Category: Androctonus]]
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| - | [[Category: Combining site]]
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| - | [[Category: Epitope]]
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| - | [[Category: Immune system]]
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| - | [[Category: Pharmacological site]]
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| - | [[Category: Scorpion]]
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| - | [[Category: Venom]]
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| - | [[Category: Voltage- activated sodium channel]]
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| Structural highlights
Publication Abstract from PubMed
The Old World scorpion Androctonus australis hector (Aah) produces one of the most lethal venoms for humans. Peptidic alpha-toxins AahI to AahIV are responsible for its potency, with AahII accounting for half of it. All four toxins are high affinity blockers of the fast inactivation phase of mammalian voltage-activated Na(+) channels. However, the high antigenic polymorphism of alpha-toxins prevents production of a polyvalent neutralizing antiserum, whereas the determinants dictating their trapping by neutralizing antibodies remain elusive. From an anti-AahII mAb, we generated an antigen binding fragment (Fab) with high affinity and selectivity for AahII and solved a 2.3 A-resolution crystal structure of the complex. Sequestering of the C-terminal region of the bound toxin within a groove formed by the Fab combining loops is associated with a toxin orientation and main and side chain conformations that dictate the AahII antigenic specificity and efficient neutralization. From an anti-AahI mAb, we also preformed and crystallized a high affinity AahI-Fab complex. The 1.6 A-resolution structure solved revealed a Fab molecule devoid of a bound AahI and with combining loops involved in packing interactions, denoting expulsion of the bound antigen upon crystal formation. Comparative analysis of the groove-like combining site of the toxin-bound anti-AahII Fab and planar combining surface of the unbound anti-AahI Fab along with complementary data from a flexible docking approach suggests occurrence of distinctive trapping orientations for the two toxins relative to their respective Fab. This study provides complementary templates for designing new molecules aimed at capturing Aah alpha-toxins and suitable for immunotherapy.
Structural Insights into Antibody Sequestering and Neutralizing of Na+ Channel alpha-Type Modulator from Old World Scorpion Venom.,Fabrichny IP, Mondielli G, Conrod S, Martin-Eauclaire MF, Bourne Y, Marchot P J Biol Chem. 2012 Apr 20;287(17):14136-48. Epub 2012 Feb 27. PMID:22371498[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Fabrichny IP, Mondielli G, Conrod S, Martin-Eauclaire MF, Bourne Y, Marchot P. Structural Insights into Antibody Sequestering and Neutralizing of Na+ Channel alpha-Type Modulator from Old World Scorpion Venom. J Biol Chem. 2012 Apr 20;287(17):14136-48. Epub 2012 Feb 27. PMID:22371498 doi:10.1074/jbc.M111.315382
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