4nc1: Difference between revisions
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==Crystal Structure of TcdA-A2 Bound to A20.1 VHH and A26.8 VHH== | ==Crystal Structure of TcdA-A2 Bound to A20.1 VHH and A26.8 VHH== | ||
<StructureSection load='4nc1' size='340' side='right' caption='[[4nc1]], [[Resolution|resolution]] 2.61Å' scene=''> | <StructureSection load='4nc1' size='340' side='right'caption='[[4nc1]], [[Resolution|resolution]] 2.61Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[4nc1]] is a 6 chain structure with sequence from [ | <table><tr><td colspan='2'>[[4nc1]] is a 6 chain structure with sequence from [https://en.wikipedia.org/wiki/Clostridioides_difficile_NAP07 Clostridioides difficile NAP07] and [https://en.wikipedia.org/wiki/Lama_glama Lama glama]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4NC1 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4NC1 FirstGlance]. <br> | ||
</td></tr><tr id=' | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.61Å</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=4nc1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4nc1 OCA], [https://pdbe.org/4nc1 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4nc1 RCSB], [https://www.ebi.ac.uk/pdbsum/4nc1 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4nc1 ProSAT]</span></td></tr> | |||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[ | |||
</table> | </table> | ||
<div style="background-color:#fffaf0;"> | <div style="background-color:#fffaf0;"> | ||
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</div> | </div> | ||
<div class="pdbe-citations 4nc1" style="background-color:#fffaf0;"></div> | <div class="pdbe-citations 4nc1" style="background-color:#fffaf0;"></div> | ||
==See Also== | |||
*[[Antibody 3D structures|Antibody 3D structures]] | |||
*[[3D structures of non-human antibody|3D structures of non-human antibody]] | |||
== References == | == References == | ||
<references/> | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: | [[Category: Clostridioides difficile NAP07]] | ||
[[Category: | [[Category: Lama glama]] | ||
[[Category: Eugenio | [[Category: Large Structures]] | ||
[[Category: Hussack | [[Category: Eugenio L]] | ||
[[Category: Kitova | [[Category: Hussack G]] | ||
[[Category: Klassen | [[Category: Kitova EN]] | ||
[[Category: Murase | [[Category: Klassen JS]] | ||
[[Category: Ng | [[Category: Murase T]] | ||
[[Category: Schorr | [[Category: Ng KKS]] | ||
[[Category: Tanha | [[Category: Schorr M]] | ||
[[Category: Tanha J]] | |||
Latest revision as of 19:52, 20 September 2023
Crystal Structure of TcdA-A2 Bound to A20.1 VHH and A26.8 VHHCrystal Structure of TcdA-A2 Bound to A20.1 VHH and A26.8 VHH
Structural highlights
Publication Abstract from PubMedClostridium difficile infection (CDI) is a serious and highly prevalent nosocomial disease in which the two large, Rho-glucosylating toxins TcdA and TcdB are the main virulence factors. We report for the first time crystal structures revealing how neutralizing and non-neutralizing single-domain antibodies (sdAbs) recognize the receptor-binding domains (RBDs) of TcdA and TcdB. Surprisingly, the complexes formed by two neutralizing antibodies recognizing TcdA do not show direct interference with the previously identified carbohydrate-binding sites, suggesting that neutralization of toxin activity may be mediated by mechanisms distinct from steric blockage of receptor binding. A camelid sdAb complex also reveals the molecular structure of the TcdB RBD for the first time, facilitating the crystallization of a strongly negatively charged protein fragment that has resisted previous attempts at crystallization and structure determination. Electrospray ionization mass spectrometry measurements confirm the stoichiometries of sdAbs observed in the crystal structures. These studies indicate how key epitopes in the RBDs from TcdA and TcdB are recognized by sdAbs, providing molecular insights into toxin structure and function, and providing for the first time a basis for the design of highly specific toxin-specific therapeutic and diagnostic agents. Structural Basis for Antibody Recognition in the Receptor-Binding Domains of Toxins A and B from Clostridium difficile.,Murase T, Eugenio L, Schorr M, Hussack G, Tanha J, Kitova EN, Klassen JS, Ng KK J Biol Chem. 2013 Dec 5. PMID:24311789[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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