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==Crystal structure of the complex between Shiga toxin Stx2 B subunit and neutralising Nb113==
<StructureSection load='6fe4' size='340' side='right' caption='[[6fe4]], [[Resolution|resolution]] 3.00&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[6fe4]] is a 10 chain structure with sequence from [http://en.wikipedia.org/wiki/Alpaca Alpaca] and [http://en.wikipedia.org/wiki/Bp933 Bp933]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6FE4 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6FE4 FirstGlance]. <br>
</td></tr><tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">stxB2, stx2B, L0104 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10730 BP933])</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=6fe4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6fe4 OCA], [http://pdbe.org/6fe4 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6fe4 RCSB], [http://www.ebi.ac.uk/pdbsum/6fe4 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6fe4 ProSAT]</span></td></tr>
</table>
== Function ==
[[http://www.uniprot.org/uniprot/STXB_BP933 STXB_BP933]] The B subunit is responsible for the binding of the holotoxin to specific receptors on the target cell surface, such as globotriaosylceramide (Gb3) in human intestinal microvilli. 
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== Publication Abstract from PubMed ==
BACKGROUND: Shiga toxin-producing Escherichia coli (STEC) are a subset of pathogens leading to illnesses such as diarrhea, hemolytic uremic syndrome and even death. The Shiga toxins are the main virulence factors and divided in two groups: Stx1 and Stx2, of which the latter is more frequently associated with severe pathologies in humans. RESULTS: An immune library of nanobodies (Nbs) was constructed after immunizing an alpaca with recombinant Shiga toxin-2a B subunit (rStx2aB), to retrieve multiple rStx2aB-specific Nbs. The specificity of five Nbs towards rStx2aB was confirmed in ELISA and Western blot. Nb113 had the highest affinity (9.6 nM) and its bivalent construct exhibited a 100-fold higher functional affinity. The structure of the Nb113 in complex with rStx2aB was determined via X-ray crystallography. The crystal structure of the Nb113-rStx2aB complex revealed that five copies of Nb113 bind to the rStx2aB pentamer and that the Nb113 epitope overlaps with the Gb3 binding site, thereby providing a structural basis for the neutralization of Stx2a by Nb113 that was observed on Vero cells. Finally, the tandem-repeated, bivalent Nb113(2) exhibits a higher toxin neutralization capacity compared to monovalent Nb113. CONCLUSIONS: The Nb of highest affinity for rStx2aB is also the best Stx2a and Stx2c toxin neutralizing Nb, especially in a bivalent format. This lead Nb neutralizes Stx2a by competing for the Gb3 receptor. The fusion of the bivalent Nb113(2) with a serum albumin specific Nb is expected to combine high toxin neutralization potential with prolonged blood circulation.

Structural Basis for the Specific Neutralization of Stx2a with a Camelid Single Domain Antibody Fragment.,Bernedo-Navarro RA, Romao E, Yano T, Pinto J, De Greve H, Sterckx YG, Muyldermans S Toxins (Basel). 2018 Mar 1;10(3). pii: toxins10030108. doi:, 10.3390/toxins10030108. PMID:29494518<ref>PMID:29494518</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
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== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Alpaca]]
[[Category: Bp933]]
[[Category: Bernedo, R]]
[[Category: Muyldermans, S]]
[[Category: Sterckx, Y G.J]]
[[Category: Complex]]
[[Category: Nanobody]]
[[Category: Shiga]]
[[Category: Toxin]]