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| | ==Glycosylated SV2 and Gangliosides as Dual Receptors for Botulinum Neurotoxin Serotype F== | | ==Glycosylated SV2 and Gangliosides as Dual Receptors for Botulinum Neurotoxin Serotype F== |
| - | <StructureSection load='3fuq' size='340' side='right' caption='[[3fuq]], [[Resolution|resolution]] 2.10Å' scene=''> | + | <StructureSection load='3fuq' size='340' side='right'caption='[[3fuq]], [[Resolution|resolution]] 2.10Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[3fuq]] is a 1 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=3FUQ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3FUQ FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[3fuq]] 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=3FUQ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3FUQ FirstGlance]. <br> |
| - | </td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3fuo|3fuo]]</td></tr> | + | </td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[3fuo|3fuo]]</div></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">bont/f, Botulinum Neurotoxin F ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=1491 "Bacillus botulinus" van Ermengem 1896])</td></tr> | + | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">bont/f, Botulinum Neurotoxin F ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=1491 "Bacillus botulinus" van Ermengem 1896])</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=3fuq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3fuq OCA], [http://pdbe.org/3fuq PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3fuq RCSB], [http://www.ebi.ac.uk/pdbsum/3fuq PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3fuq 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=3fuq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3fuq OCA], [https://pdbe.org/3fuq PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3fuq RCSB], [https://www.ebi.ac.uk/pdbsum/3fuq PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3fuq ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Evolutionary Conservation == | | == Evolutionary Conservation == |
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| | </div> | | </div> |
| | <div class="pdbe-citations 3fuq" style="background-color:#fffaf0;"></div> | | <div class="pdbe-citations 3fuq" style="background-color:#fffaf0;"></div> |
| | + | |
| | + | ==See Also== |
| | + | *[[Botulinum neurotoxin 3D structures|Botulinum neurotoxin 3D structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
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| | </StructureSection> | | </StructureSection> |
| | [[Category: Bacillus botulinus van ermengem 1896]] | | [[Category: Bacillus botulinus van ermengem 1896]] |
| | + | [[Category: Large Structures]] |
| | [[Category: Baldwin, M R]] | | [[Category: Baldwin, M R]] |
| | [[Category: Barbieri, J T]] | | [[Category: Barbieri, J T]] |
| Structural highlights
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 neurotoxin causes rapid flaccid paralysis through the inhibition of acetylcholine release at the neuromuscular junction. The seven BoNT serotypes (A-G) have been proposed to bind motor neurons via ganglioside-protein dual receptors. To date, the structure-function properties of BoNT/F host receptor interactions have not been resolved. Here, we report the crystal structures of the receptor binding domains (HCR) of BoNT/A and BoNT/F and the characterization of the dual receptors for BoNT/F. The overall polypeptide fold of HCR/A is essentially identical to the receptor binding domain of the BoNT/A holotoxin, and the structure of HCR/F is very similar to that of HCR/A, except for two regions implicated in neuronal binding. Solid phase array analysis identified two HCR/F binding glycans: ganglioside GD1a and oligosaccharides containing an N-acetyllactosamine core. Using affinity chromatography, HCR/F bound native synaptic vesicle glycoproteins as part of a protein complex. Deglycosylation of glycoproteins using alpha(1-3,4)-fucosidase, endo-beta-galactosidase, and PNGase F disrupted the interaction with HCR/F, while the binding of HCR/B to its cognate receptor, synaptotagmin I, was unaffected. These data indicate that the HCR/F binds synaptic vesicle glycoproteins through the keratan sulfate moiety of SV2. The interaction of HCR/F with gangliosides was also investigated. HCR/F bound specifically to gangliosides that contain alpha2,3-linked sialic acid on the terminal galactose of a neutral saccharide core (binding order GT1b = GD1a >> GM3; no binding to GD1b and GM1a). Mutations within the putative ganglioside binding pocket of HCR/F decreased binding to gangliosides, synaptic vesicle protein complexes, and primary rat hippocampal neurons. Thus, BoNT/F neuronal discrimination involves the recognition of ganglioside and protein (glycosylated SV2) carbohydrate moieties, providing a structural basis for the high affinity and specificity of BoNT/F for neurons.
Glycosylated SV2 and Gangliosides as Dual Receptors for Botulinum Neurotoxin Serotype F.,Fu Z, Chen C, Barbieri JT, Kim JJ, Baldwin MR Biochemistry. 2009 Jun 23;48(24):5631-41. PMID:19476346[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Fu Z, Chen C, Barbieri JT, Kim JJ, Baldwin MR. Glycosylated SV2 and Gangliosides as Dual Receptors for Botulinum Neurotoxin Serotype F. Biochemistry. 2009 Jun 23;48(24):5631-41. PMID:19476346 doi:10.1021/bi9002138
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