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6es1

From Proteopedia

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Current revision

Crystal structure of the binding domain from botulinum neurotoxin A2 bound to extracellular domain of human receptor SV2C

Structural highlights

6es1 is a 2 chain structure. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:
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

Botulinum neurotoxins (BoNTs) are a family of highly dangerous bacterial toxins, with seven major serotypes (BoNT/A-G). Members of BoNTs, BoNT/A1 and BoNT/B1, have been utilized to treat an increasing number of medical conditions. The clinical trials are ongoing for BoNT/A2, another subtype of BoNT/A, which showed promising therapeutic properties. Both BoNT/A1 and BoNT/A2 utilize three isoforms of synaptic vesicle protein SV2 (SV2A, B, and C) as their protein receptors. We here present a high resolution (2.0 A) co-crystal structure of the BoNT/A2 receptor-binding domain in complex with the human SV2C luminal domain. The structure is similar to previously reported BoNT/A-SV2C complexes, but a shift of the receptor-binding segment in BoNT/A2 rotates SV2C in two dimensions giving insight into the dynamic behavior of the interaction. Small differences in key residues at the binding interface may influence the binding to different SV2 isoforms, which may contribute to the differences between BoNT/A1 and BoNT/A2 observed in the clinic.

Crystal Structure of Botulinum Neurotoxin A2 in Complex with the Human Protein Receptor SV2C Reveals Plasticity in Receptor Binding.,Gustafsson R, Zhang S, Masuyer G, Dong M, Stenmark P Toxins (Basel). 2018 Apr 12;10(4). pii: toxins10040153. doi:, 10.3390/toxins10040153. PMID:29649119^[1]

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

References

↑ Gustafsson R, Zhang S, Masuyer G, Dong M, Stenmark P. Crystal Structure of Botulinum Neurotoxin A2 in Complex with the Human Protein Receptor SV2C Reveals Plasticity in Receptor Binding. Toxins (Basel). 2018 Apr 12;10(4). pii: toxins10040153. doi:, 10.3390/toxins10040153. PMID:29649119 doi:http://dx.doi.org/10.3390/toxins10040153

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/6es1"

@@ Line 1: / Line 1: @@
 ==Crystal structure of the binding domain from botulinum neurotoxin A2 bound to extracellular domain of human receptor SV2C==
-<StructureSection load='6es1' size='340' side='right' caption='[[6es1]], [[Resolution|resolution]] 2.00&Aring;' scene=''>
+<StructureSection load='6es1' size='340' side='right'caption='[[6es1]], [[Resolution|resolution]] 2.00&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[6es1]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6ES1 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6ES1 FirstGlance]. <br>
+<table><tr><td colspan='2'>[[6es1]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6ES1 OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6ES1 FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene></td></tr>
+</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene></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=6es1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6es1 OCA], [http://pdbe.org/6es1 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6es1 RCSB], [http://www.ebi.ac.uk/pdbsum/6es1 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6es1 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=6es1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6es1 OCA], [http://pdbe.org/6es1 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6es1 RCSB], [http://www.ebi.ac.uk/pdbsum/6es1 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6es1 ProSAT]</span></td></tr>
 </table>
 == Function ==
@@ Line 19: / Line 19: @@
 </div>
 <div class="pdbe-citations 6es1" style="background-color:#fffaf0;"></div>
+==See Also==
+*[[Botulinum neurotoxin 3D structures|Botulinum neurotoxin 3D structures]]
 == References ==
 <references/>
@@ Line 24: / Line 27: @@
 </StructureSection>
 [[Category: Bontoxilysin]]
+[[Category: Large Structures]]
 [[Category: Gustafsson, R]]
 [[Category: Masuyer, G]]

6es1

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Current revision

Crystal structure of the binding domain from botulinum neurotoxin A2 bound to extracellular domain of human receptor SV2C

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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