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| | ==Crystal structure of HCR/D-Sa-GBL1/C== | | ==Crystal structure of HCR/D-Sa-GBL1/C== |
| - | <StructureSection load='4fvv' size='340' side='right' caption='[[4fvv]], [[Resolution|resolution]] 2.70Å' scene=''> | + | <StructureSection load='4fvv' size='340' side='right'caption='[[4fvv]], [[Resolution|resolution]] 2.70Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4fvv]] is a 2 chain structure with sequence from [http://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=4FVV OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4FVV FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4fvv]] is a 2 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=4FVV OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4FVV FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=SIA:O-SIALIC+ACID'>SIA</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></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]] 2.7Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3n7l|3n7l]]</td></tr>
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=SIA:O-SIALIC+ACID'>SIA</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'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4fvv FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4fvv OCA], [http://pdbe.org/4fvv PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4fvv RCSB], [http://www.ebi.ac.uk/pdbsum/4fvv PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4fvv 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=4fvv FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4fvv OCA], [https://pdbe.org/4fvv PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4fvv RCSB], [https://www.ebi.ac.uk/pdbsum/4fvv PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4fvv ProSAT]</span></td></tr> |
| | </table> | | </table> |
| - | <div style="background-color:#fffaf0;">
| + | == Function == |
| - | == Publication Abstract from PubMed == | + | [https://www.uniprot.org/uniprot/Q9LBR1_CLOBO Q9LBR1_CLOBO] |
| - | Botulinum neurotoxins (BoNTs) cleave SNARE proteins in motor neurons that inhibits synaptic vesicle (SV) exocytosis, resulting in flaccid paralysis. There are seven BoNT serotypes (A-G). In current models, BoNTs initially bind gangliosides on resting neurons and upon SV exocytosis associate with the luminal domains of SV-associated proteins as a second receptor. The entry of BoNT/C is less clear. Characterizing the heavy chain receptor binding domain (HCR), BoNT/C was shown to utilize gangliosides as dual host receptors. Crystallographic and biochemical studies showed that the two ganglioside binding sites, termed GBP2 and Sia-1, were independent and utilized unique mechanisms to bind complex gangliosides. The GBP2 binding site recognized gangliosides that contained a sia5 sialic acid, whereas the Sia-1 binding site recognized gangliosides that contained a sia7 sialic acid and sugars within the backbone of the ganglioside. Utilizing gangliosides that uniquely recognized the GBP2 and Sia-1 binding sites, HCR/C entry into Neuro-2A cells required both functional ganglioside binding sites. HCR/C entered cells differently than the HCR of tetanus toxin, which also utilizes dual gangliosides as host receptors. A point-mutated HCR/C that lacked GBP2 binding potential retained the ability to bind and enter Neuro-2A cells. This showed that ganglioside binding at the Sia-1 site was accessible on the plasma membrane, suggesting that SV exocytosis may not be required to expose BoNT/C receptors. These studies highlight the utility of BoNT HCRs as probes to study the role of gangliosides in neurotransmission.
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| - | Botulinum neurotoxin serotype C associates with dual ganglioside receptors to facilitate cell entry.,Karalewitz AP, Fu Z, Baldwin MR, Kim JJ, Barbieri JT J Biol Chem. 2012 Nov 23;287(48):40806-16. doi: 10.1074/jbc.M112.404244. Epub, 2012 Oct 1. PMID:23027864<ref>PMID:23027864</ref>
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| - | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
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| - | </div>
| + | |
| - | <div class="pdbe-citations 4fvv" style="background-color:#fffaf0;"></div>
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| - | == References ==
| + | |
| - | <references/>
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Bacillus botulinus van ermengem 1896]] | + | [[Category: Clostridium botulinum]] |
| - | [[Category: Baldwin, M R]] | + | [[Category: Large Structures]] |
| - | [[Category: Barbieri, J T]] | + | [[Category: Baldwin MR]] |
| - | [[Category: Fu, Z]] | + | [[Category: Barbieri JT]] |
| - | [[Category: Karalewitz, A]] | + | [[Category: Fu Z]] |
| - | [[Category: Kim, J J.P]] | + | [[Category: Karalewitz A]] |
| - | [[Category: Botulinum toxin]]
| + | [[Category: Kim J-JP]] |
| - | [[Category: Ganglioside]]
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| - | [[Category: Ganglioside bing loop]]
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| - | [[Category: Toxin]]
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