9f25
From Proteopedia
(Difference between revisions)
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| - | '''Unreleased structure''' | ||
| - | + | ==Cryo-EM structure of Botulinum neurotoxin A LC-HN domain== | |
| + | <StructureSection load='9f25' size='340' side='right'caption='[[9f25]], [[Resolution|resolution]] 3.70Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[9f25]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Clostridium_botulinum Clostridium botulinum]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=9F25 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=9F25 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]] 3.7Å</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=9f25 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=9f25 OCA], [https://pdbe.org/9f25 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=9f25 RCSB], [https://www.ebi.ac.uk/pdbsum/9f25 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=9f25 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 A1 (BoNT/A1) belongs to the most potent toxins and is used as a major therapeutic agent. Neurotoxin conformation is crucial for its translocation to the neuronal cytosol, a key process for intoxication that is only poorly understood. To gain molecular insights into the steps preceding toxin translocation, we determine cryo-EM structures of BoNT/A1 alone and in complex with its receptor synaptic vesicle glycoprotein 2B (SV2B). In solution, BoNT/A1 adopts a unique, semi-closed conformation. The toxin changes its structure into an open state upon receptor binding with the translocation domain (H(N)) and the catalytic domain (LC) remote from the membrane, suggesting translocation incompatibility. Under acidic pH conditions, where translocation is initiated, receptor-bound BoNT/A1 switches back into a semi-closed conformation. This conformation brings the LC and H(N) close to the membrane, suggesting that a translocation-competent state of the toxin is required for successful LC transport into the neuronal cytosol. | ||
| - | + | Cryo-EM structure of the botulinum neurotoxin A/SV2B complex and its implications for translocation.,Khanppnavar B, Leka O, Pal SK, Korkhov VM, Kammerer RA Nat Commun. 2025 Feb 11;16(1):1224. doi: 10.1038/s41467-025-56304-z. PMID:39934119<ref>PMID:39934119</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | [[Category: | + | </div> |
| + | <div class="pdbe-citations 9f25" style="background-color:#fffaf0;"></div> | ||
| + | == References == | ||
| + | <references/> | ||
| + | __TOC__ | ||
| + | </StructureSection> | ||
| + | [[Category: Clostridium botulinum]] | ||
| + | [[Category: Large Structures]] | ||
| + | [[Category: Kammerer R]] | ||
| + | [[Category: Khanppnavar B]] | ||
| + | [[Category: Korkhov V]] | ||
| + | [[Category: Leka O]] | ||
Current revision
Cryo-EM structure of Botulinum neurotoxin A LC-HN domain
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