5moy

From Proteopedia

(Difference between revisions)

Revision as of 07:25, 19 August 2020

Crystal structure of the BoNT/A2 receptor-binding domain in complex with the luminal domain of its neuronal receptor SV2C

Structural highlights

5moy is a 2 chain structure with sequence from "bacillus_botulinus"_van_ermengem_1896 "bacillus botulinus" van ermengem 1896 and Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	,
Related:	4jra
Gene:	botA, atx, bna ("Bacillus botulinus" van Ermengem 1896), SV2C, KIAA1054 (HUMAN)
Activity:	Bontoxilysin, with EC number 3.4.24.69
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[BXA2_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 the three isoforms 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 (By similarity). [SV2C_HUMAN] Plays a role in the control of regulated secretion in neural and endocrine cells, enhancing selectively low-frequency neurotransmission. Positively regulates vesicle fusion by maintaining the readily releasable pool of secretory vesicles (By similarity).

Publication Abstract from PubMed

A detailed molecular understanding of botulinum neurotoxin (BoNT)/host-cell-receptor interactions is fundamental both for developing strategies against botulism and for generating improved BoNT variants for medical applications. The X-ray crystal structure of the receptor-binding domain (HC) of BoNT/A1 in complex with the luminal domain (LD) of its neuronal receptor SV2C revealed only few specific side-chain - side-chain interactions that are important for binding. Notably, two BoNT/A1 residues, Arg 1156 and Arg 1294, that are crucial for the interaction with SV2, are not conserved among subtypes. Because it has been suggested that differential receptor binding of subtypes might explain their differences in biological activity, we determined the crystal structure of BoNT/A2-HC in complex with SV2C-LD. Although only few side-chain interactions are conserved between the two BoNT/A subtypes, the overall binding mode of subtypes A1 and A2 is virtually identical. In the BoNT/A2-HC - SV2C complex structure, a missing cation-pi stacking is compensated for by an additional salt bridge and an anion-pi stacking interaction, which explains why the binding of BoNT/A subtypes to SV2C tolerates variable side chains. These findings suggest that motif extensions and a shallow binding cleft in BoNT/A-HC contribute to binding specificity.

Crystal structure of the BoNT/A2 receptor-binding domain in complex with the luminal domain of its neuronal receptor SV2C.,Benoit RM, Scharer MA, Wieser MM, Li X, Frey D, Kammerer RA Sci Rep. 2017 Mar 2;7:43588. doi: 10.1038/srep43588. PMID:28252640^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Benoit RM, Scharer MA, Wieser MM, Li X, Frey D, Kammerer RA. Crystal structure of the BoNT/A2 receptor-binding domain in complex with the luminal domain of its neuronal receptor SV2C. Sci Rep. 2017 Mar 2;7:43588. doi: 10.1038/srep43588. PMID:28252640 doi:http://dx.doi.org/10.1038/srep43588

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 See Also
5 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/5moy"

@@ Line 1: / Line 1: @@
 ==Crystal structure of the BoNT/A2 receptor-binding domain in complex with the luminal domain of its neuronal receptor SV2C==
-<StructureSection load='5moy' size='340' side='right' caption='[[5moy]], [[Resolution|resolution]] 2.30&Aring;' scene=''>
+<StructureSection load='5moy' size='340' side='right'caption='[[5moy]], [[Resolution|resolution]] 2.30&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[5moy]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5MOY OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5MOY FirstGlance]. <br>
+<table><tr><td colspan='2'>[[5moy]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/"bacillus_botulinus"_van_ermengem_1896 "bacillus botulinus" van ermengem 1896] and [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5MOY OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=5MOY FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=2PE:NONAETHYLENE+GLYCOL'>2PE</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene></td></tr>
+</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=2PE:NONAETHYLENE+GLYCOL'>2PE</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene></td></tr>
 <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4jra|4jra]]</td></tr>
+<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">botA, atx, bna ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=1491 "Bacillus botulinus" van Ermengem 1896]), SV2C, KIAA1054 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
 <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Bontoxilysin Bontoxilysin], with EC number [http://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'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5moy FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5moy OCA], [http://pdbe.org/5moy PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5moy RCSB], [http://www.ebi.ac.uk/pdbsum/5moy PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5moy ProSAT]</span></td></tr>
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=5moy FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5moy OCA], [http://pdbe.org/5moy PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5moy RCSB], [http://www.ebi.ac.uk/pdbsum/5moy PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5moy ProSAT]</span></td></tr>
 </table>
 == Function ==
@@ Line 20: / Line 21: @@
 </div>
 <div class="pdbe-citations 5moy" style="background-color:#fffaf0;"></div>
+==See Also==
+*[[Botulinum neurotoxin 3D structures|Botulinum neurotoxin 3D structures]]
 == References ==
 <references/>
 __TOC__
 </StructureSection>
+[[Category: Bacillus botulinus van ermengem 1896]]
 [[Category: Bontoxilysin]]
+[[Category: Human]]
+[[Category: Large Structures]]
 [[Category: Benoit, R M]]
 [[Category: Scharer, M A]]

5moy

From Proteopedia

Revision as of 07:25, 19 August 2020

Crystal structure of the BoNT/A2 receptor-binding domain in complex with the luminal domain of its neuronal receptor SV2C

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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