9ea9
From Proteopedia
(Difference between revisions)
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| - | '''Unreleased structure''' | ||
| - | + | ==Crystal structure of BoNT/A-NTNH-HA70 -VHH_F12-VHH_H7-Fab_NTNH complex== | |
| + | <StructureSection load='9ea9' size='340' side='right'caption='[[9ea9]], [[Resolution|resolution]] 2.93Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[9ea9]] is a 14 chain structure with sequence from [https://en.wikipedia.org/wiki/Clostridium_botulinum Clostridium botulinum], [https://en.wikipedia.org/wiki/Mus_sp. Mus sp.] 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=9EA9 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=9EA9 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]] 2.93Å</td></tr> | ||
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</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=9ea9 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=9ea9 OCA], [https://pdbe.org/9ea9 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=9ea9 RCSB], [https://www.ebi.ac.uk/pdbsum/9ea9 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=9ea9 ProSAT]</span></td></tr> | ||
| + | </table> | ||
| + | == Function == | ||
| + | [https://www.uniprot.org/uniprot/BXA1_CLOBO BXA1_CLOBO] Inhibits acetylcholine release. The botulinum toxin binds with high affinity to peripheral neuronal presynaptic membrane to the secretory vesicle protein SV2. It binds directly to the largest luminal loop of SV2A, SV2B and SV2C. It is then internalized by receptor-mediated endocytosis. The C-terminus of the heavy chain (H) is responsible for the adherence of the toxin to the cell surface while the N-terminus mediates transport of the light chain from the endocytic vesicle to the cytosol. After translocation, the light chain (L) hydrolyzes the 197-Gln-|-Arg-198 bond in SNAP-25, thereby blocking neurotransmitter release. Inhibition of acetylcholine release results in flaccid paralysis, with frequent heart or respiratory failure. | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | Botulinum neurotoxin serotype A (BoNT/A) is naturally produced by bacteria along with four nontoxic neurotoxin-associated proteins (NTNH, HA70, HA33, and HA17), forming a bimodular large progenitor toxin complex (L-PTC). The BoNT/A-NTNH complex protects the toxin from adverse environment, while the complex consisting of HA proteins facilitates toxin absorption during oral intoxication. How these two independent modules assemble into the L-PTC remains unclear. Here, we report the crystal structure of the BoNT/A-NTNH-HA70 complex at ~2.9-A resolution. The structure reveals that the BoNT/A-NTNH complex is anchored into a concentric double beta-barrel channel of trimeric HA70 through a short beta-hairpin of NTNH (termed nLoop), resembling a nut-and-bolt attachment. We find that the nLoop of NTNH is strictly conserved across HA-containing BoNT complexes and that NTNH-HA70 binding is interchangeable among them. Furthermore, we demonstrate that the nLoop functions as a minimal motif enabling attachment of a protein-of-interest to the HA complex, with potential applications in oral biologics delivery. | ||
| - | + | A nut-and-bolt assembly of the bimodular large progenitor botulinum neurotoxin complex.,Lam KH, Gao L, Przykopanski A, Chen B, Huang T, Kruger M, Bartels AM, Dorner MB, Perry K, Dorner BG, Rummel A, Jin R Sci Adv. 2025 Aug 29;11(35):eadx5831. doi: 10.1126/sciadv.adx5831. Epub 2025 Aug , 27. PMID:40864694<ref>PMID:40864694</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | [[Category: | + | </div> |
| + | <div class="pdbe-citations 9ea9" style="background-color:#fffaf0;"></div> | ||
| + | == References == | ||
| + | <references/> | ||
| + | __TOC__ | ||
| + | </StructureSection> | ||
| + | [[Category: Clostridium botulinum]] | ||
| + | [[Category: Large Structures]] | ||
| + | [[Category: Mus sp]] | ||
| + | [[Category: Vicugna pacos]] | ||
| + | [[Category: Gao L]] | ||
| + | [[Category: Jin R]] | ||
| + | [[Category: Lam KH]] | ||
Current revision
Crystal structure of BoNT/A-NTNH-HA70 -VHH_F12-VHH_H7-Fab_NTNH complex
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