5lr0: Difference between revisions
New page: '''Unreleased structure''' The entry 5lr0 is ON HOLD Authors: Description: Category: Unreleased Structures |
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==Binding domain of Botulinum Neurotoxin DC in complex with SialylT== | |||
<StructureSection load='5lr0' size='340' side='right'caption='[[5lr0]], [[Resolution|resolution]] 2.59Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[5lr0]] 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=5LR0 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5LR0 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]] 2.59Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GAL:BETA-D-GALACTOSE'>GAL</scene>, <scene name='pdbligand=NGA:N-ACETYL-D-GALACTOSAMINE'>NGA</scene>, <scene name='pdbligand=SIA:O-SIALIC+ACID'>SIA</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=5lr0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5lr0 OCA], [https://pdbe.org/5lr0 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5lr0 RCSB], [https://www.ebi.ac.uk/pdbsum/5lr0 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5lr0 ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/A5JGM8_CLOBO A5JGM8_CLOBO] | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Botulinum neurotoxins (BoNTs), the most potent toxins known, are potential bioterrorism agents. It is well established that all seven serotypes of BoNTs (BoNT/A-G) require complex gangliosides as co-receptors. Here, we report that BoNT/DC, a presumed mosaic toxin between BoNT/D and BoNT/C1, binds and enters efficiently into neurons lacking complex gangliosides and shows no reduction in toxicity in mice deficient in complex gangliosides. The co-crystal structure of BoNT/DC with sialyl-Thomsen-Friedenreich antigen (Sialyl-T) suggests that BoNT/DC recognizes only the sialic acid, but not other moieties in gangliosides. Using liposome flotation assays, we demonstrate that an extended loop in BoNT/DC directly interacts with lipid membranes, and the co-occurring sialic acid binding and loop-membrane interactions mediate the recognition of gangliosides in membranes by BoNT/DC. These findings reveal a unique mechanism for cell membrane recognition and demonstrate that BoNT/DC can use a broad range of sialic acid-containing moieties as co-receptors. | |||
Structural basis for the unique ganglioside and cell membrane recognition mechanism of botulinum neurotoxin DC.,Zhang S, Berntsson RP, Tepp WH, Tao L, Johnson EA, Stenmark P, Dong M Nat Commun. 2017 Nov 21;8(1):1637. doi: 10.1038/s41467-017-01534-z. PMID:29158482<ref>PMID:29158482</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
<div class="pdbe-citations 5lr0" style="background-color:#fffaf0;"></div> | |||
==See Also== | |||
*[[Botulinum neurotoxin 3D structures|Botulinum neurotoxin 3D structures]] | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Clostridium botulinum]] | |||
[[Category: Large Structures]] | |||
[[Category: Berntsson RP-A]] | |||
[[Category: Stenmark P]] | |||
Latest revision as of 21:41, 18 October 2023
Binding domain of Botulinum Neurotoxin DC in complex with SialylTBinding domain of Botulinum Neurotoxin DC in complex with SialylT
Structural highlights
FunctionPublication Abstract from PubMedBotulinum neurotoxins (BoNTs), the most potent toxins known, are potential bioterrorism agents. It is well established that all seven serotypes of BoNTs (BoNT/A-G) require complex gangliosides as co-receptors. Here, we report that BoNT/DC, a presumed mosaic toxin between BoNT/D and BoNT/C1, binds and enters efficiently into neurons lacking complex gangliosides and shows no reduction in toxicity in mice deficient in complex gangliosides. The co-crystal structure of BoNT/DC with sialyl-Thomsen-Friedenreich antigen (Sialyl-T) suggests that BoNT/DC recognizes only the sialic acid, but not other moieties in gangliosides. Using liposome flotation assays, we demonstrate that an extended loop in BoNT/DC directly interacts with lipid membranes, and the co-occurring sialic acid binding and loop-membrane interactions mediate the recognition of gangliosides in membranes by BoNT/DC. These findings reveal a unique mechanism for cell membrane recognition and demonstrate that BoNT/DC can use a broad range of sialic acid-containing moieties as co-receptors. Structural basis for the unique ganglioside and cell membrane recognition mechanism of botulinum neurotoxin DC.,Zhang S, Berntsson RP, Tepp WH, Tao L, Johnson EA, Stenmark P, Dong M Nat Commun. 2017 Nov 21;8(1):1637. doi: 10.1038/s41467-017-01534-z. PMID:29158482[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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