9mr7
From Proteopedia
(Difference between revisions)
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| - | '''Unreleased structure''' | ||
| - | + | ==Genetiocally detoxified pertussis toxin in complex with hu1B7 Fab and hu11E6 Fab== | |
| + | <StructureSection load='9mr7' size='340' side='right'caption='[[9mr7]], [[Resolution|resolution]] 3.56Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[9mr7]] is a 12 chain structure with sequence from [https://en.wikipedia.org/wiki/Bordetella_pertussis Bordetella pertussis] and [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=9MR7 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=9MR7 FirstGlance]. <br> | ||
| + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 3.56Å</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=9mr7 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=9mr7 OCA], [https://pdbe.org/9mr7 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=9mr7 RCSB], [https://www.ebi.ac.uk/pdbsum/9mr7 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=9mr7 ProSAT]</span></td></tr> | ||
| + | </table> | ||
| + | == Function == | ||
| + | [https://www.uniprot.org/uniprot/TOX1_BORPE TOX1_BORPE] S1 is an NAD-dependent ADP-ribosyltransferase, which plays a crucial role in the pathogenesis of B.pertussis causing disruption of normal host cellular regulation. It catalyzes the ADP-ribosylation of a cysteine in the alpha subunit of host heterotrimeric G proteins. In the absence of G proteins it also catalyzes the cleavage of NAD(+) into ADP-ribose and nicotinamide. It irreversibly uncouples the G-alpha GTP-binding proteins from their membrane receptors. | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | Pertussis toxin (PT) is a key protective antigen in vaccine- and natural immunity-mediated protection from Bordetella pertussis infection. Despite its importance, no PT-neutralizing epitopes have been characterized structurally. To define neutralizing epitopes and identify key structural elements to preserve during PT antigen design, we determined a 3.6 A cryoelectron microscopy structure of genetically detoxified PT (PTg) bound to hu11E6 and hu1B7, two potently neutralizing anti-PT antibodies with complementary mechanisms: disruption of toxin adhesion to cells and intracellular activities, respectively. Hu11E6 binds the paralogous S2 and S3 subunits of PTg via a conserved epitope but surprisingly did not span the previously identified sialic acid-binding site implicated in toxin adhesion. Hu11E6 specifically prevented PTg binding to sialylated N-glycans and a sialylated model receptor, as demonstrated by high-throughput glycan array analysis and ELISA, while a T cell activation assay showed that it blocks PTg mitogenic activities to define its neutralizing mechanism. Hu1B7 bound a quaternary epitope spanning the S1 and S5 subunits, although functional studies of hu1B7 variants suggested that S5 binding is not involved in its PT neutralization mechanism. These results structurally define neutralizing epitopes on PT, improving our molecular understanding of immune protection from B. pertussis and providing key information for the future development of PT immunogens. | ||
| - | + | Structural basis for neutralizing antibody binding to pertussis toxin.,Goldsmith JA, Nguyen AW, Wilen RE, Wijagkanalan W, McLellan JS, Maynard JA Proc Natl Acad Sci U S A. 2025 Apr 8;122(14):e2419457122. doi: , 10.1073/pnas.2419457122. Epub 2025 Apr 2. PMID:40172968<ref>PMID:40172968</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | [[Category: | + | </div> |
| + | <div class="pdbe-citations 9mr7" style="background-color:#fffaf0;"></div> | ||
| + | == References == | ||
| + | <references/> | ||
| + | __TOC__ | ||
| + | </StructureSection> | ||
| + | [[Category: Bordetella pertussis]] | ||
| + | [[Category: Large Structures]] | ||
| + | [[Category: Mus musculus]] | ||
| + | [[Category: Goldsmith JA]] | ||
| + | [[Category: McLellan JS]] | ||
Current revision
Genetiocally detoxified pertussis toxin in complex with hu1B7 Fab and hu11E6 Fab
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