View source for 7uia


==Crystal structure of BoNT/E receptor binding domain in complex with SV2 and VHH==
<StructureSection load='7uia' size='340' side='right'caption='[[7uia]], [[Resolution|resolution]] 2.59&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[7uia]] is a 6 chain structure with sequence from [https://en.wikipedia.org/wiki/Clostridium_botulinum Clostridium botulinum], [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Vicugna_pacos Vicugna pacos]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7UIA OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7UIA FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.59&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=PEG:DI(HYDROXYETHYL)ETHER'>PEG</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></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=7uia FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7uia OCA], [https://pdbe.org/7uia PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7uia RCSB], [https://www.ebi.ac.uk/pdbsum/7uia PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7uia ProSAT]</span></td></tr>
</table>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Botulinum neurotoxin E (BoNT/E) is one of the major causes of human botulism and paradoxically also a promising therapeutic agent. Here we determined the co-crystal structures of the receptor-binding domain of BoNT/E (H(C)E) in complex with its neuronal receptor synaptic vesicle glycoprotein 2A (SV2A) and a nanobody that serves as a ganglioside surrogate. These structures reveal that the protein-protein interactions between H(C)E and SV2 provide the crucial location and specificity information for H(C)E to recognize SV2A and SV2B, but not the closely related SV2C. At the same time, H(C)E exploits a separated sialic acid-binding pocket to mediate recognition of an N-glycan of SV2. Structure-based mutagenesis and functional studies demonstrate that both the protein-protein and protein-glycan associations are essential for SV2A-mediated cell entry of BoNT/E and for its potent neurotoxicity. Our studies establish the structural basis to understand the receptor-specificity of BoNT/E and to engineer BoNT/E variants for new clinical applications.

Structural basis for botulinum neurotoxin E recognition of synaptic vesicle protein 2.,Liu Z, Lee PG, Krez N, Lam KH, Liu H, Przykopanski A, Chen P, Yao G, Zhang S, Tremblay JM, Perry K, Shoemaker CB, Rummel A, Dong M, Jin R Nat Commun. 2023 Apr 24;14(1):2338. doi: 10.1038/s41467-023-37860-8. PMID:37095076<ref>PMID:37095076</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 7uia" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Clostridium botulinum]]
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Vicugna pacos]]
[[Category: Chen P]]
[[Category: Jin R]]
[[Category: Liu Z]]