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| | <StructureSection load='2vua' size='340' side='right'caption='[[2vua]], [[Resolution|resolution]] 1.70Å' scene=''> | | <StructureSection load='2vua' size='340' side='right'caption='[[2vua]], [[Resolution|resolution]] 1.70Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[2vua]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/"bacillus_botulinus"_van_ermengem_1896 "bacillus botulinus" van ermengem 1896]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2VUA OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2VUA FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[2vua]] 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=2VUA OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2VUA FirstGlance]. <br> |
| - | </td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[3bta|3bta]], [[1uee|1uee]], [[2vu9|2vu9]]</div></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.7Å</td></tr> |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/Bontoxilysin Bontoxilysin], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.24.69 3.4.24.69] </span></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=2vua FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2vua OCA], [https://pdbe.org/2vua PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2vua RCSB], [https://www.ebi.ac.uk/pdbsum/2vua PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2vua ProSAT]</span></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=2vua FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2vua OCA], [https://pdbe.org/2vua PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2vua RCSB], [https://www.ebi.ac.uk/pdbsum/2vua PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2vua ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | + | == Function == |
| | + | [https://www.uniprot.org/uniprot/BXA1_CLOBH BXA1_CLOBH] 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. |
| | == Evolutionary Conservation == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Bacillus botulinus van ermengem 1896]] | + | [[Category: Clostridium botulinum]] |
| - | [[Category: Bontoxilysin]]
| + | |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Dupuy, J]] | + | [[Category: Dupuy J]] |
| - | [[Category: Stenmark, P]] | + | [[Category: Stenmark P]] |
| - | [[Category: Stevens, R C]] | + | [[Category: Stevens RC]] |
| - | [[Category: Ganglioside]]
| + | |
| - | [[Category: Hydrolase]]
| + | |
| - | [[Category: Membrane]]
| + | |
| - | [[Category: Metal-binding]]
| + | |
| - | [[Category: Metalloprotease]]
| + | |
| - | [[Category: Neurotoxin]]
| + | |
| - | [[Category: Protease]]
| + | |
| - | [[Category: Receptor]]
| + | |
| - | [[Category: Secreted]]
| + | |
| - | [[Category: Toxin]]
| + | |
| Structural highlights
Function
BXA1_CLOBH 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.
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
Botulinum neurotoxins have a very high affinity and specificity for their target cells requiring two different co-receptors located on the neuronal cell surface. Different toxin serotypes have different protein receptors; yet, most share a common ganglioside co-receptor, GT1b. We determined the crystal structure of the botulinum neurotoxin serotype A binding domain (residues 873-1297) alone and in complex with a GT1b analog at 1.7 A and 1.6 A, respectively. The ganglioside GT1b forms several key hydrogen bonds to conserved residues and binds in a shallow groove lined by Tryptophan 1266. GT1b binding does not induce any large structural changes in the toxin; therefore, it is unlikely that allosteric effects play a major role in the dual receptor recognition. Together with the previously published structures of botulinum neurotoxin serotype B in complex with its protein co-receptor, we can now generate a detailed model of botulinum neurotoxin's interaction with the neuronal cell surface. The two branches of the GT1b polysaccharide, together with the protein receptor site, impose strict geometric constraints on the mode of interaction with the membrane surface and strongly support a model where one end of the 100 A long translocation domain helix bundle swing into contact with the membrane, initiating the membrane anchoring event.
Crystal structure of botulinum neurotoxin type A in complex with the cell surface co-receptor GT1b-insight into the toxin-neuron interaction.,Stenmark P, Dupuy J, Imamura A, Kiso M, Stevens RC PLoS Pathog. 2008 Aug 15;4(8):e1000129. PMID:18704164[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Stenmark P, Dupuy J, Imamura A, Kiso M, Stevens RC. Crystal structure of botulinum neurotoxin type A in complex with the cell surface co-receptor GT1b-insight into the toxin-neuron interaction. PLoS Pathog. 2008 Aug 15;4(8):e1000129. PMID:18704164 doi:10.1371/journal.ppat.1000129
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