2vu9

From Proteopedia

(Difference between revisions)

Current revision

CRYSTAL STRUCTURE OF BOTULINUM NEUROTOXIN SEROTYPE A BINDING DOMAIN IN COMPLEX WITH GT1B

Structural highlights

2vu9 is a 1 chain structure with sequence from Clostridium botulinum A. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 1.6Å
Ligands:	, , , ,
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

BXA1_CLOBH 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 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.

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 neurotoxins have a very high affinity and specificity for their target cells requiring two different co-receptors located on the neuronal cell surface. Different toxin serotypes have different protein receptors; yet, most share a common ganglioside co-receptor, GT1b. We determined the crystal structure of the botulinum neurotoxin serotype A binding domain (residues 873-1297) alone and in complex with a GT1b analog at 1.7 A and 1.6 A, respectively. The ganglioside GT1b forms several key hydrogen bonds to conserved residues and binds in a shallow groove lined by Tryptophan 1266. GT1b binding does not induce any large structural changes in the toxin; therefore, it is unlikely that allosteric effects play a major role in the dual receptor recognition. Together with the previously published structures of botulinum neurotoxin serotype B in complex with its protein co-receptor, we can now generate a detailed model of botulinum neurotoxin's interaction with the neuronal cell surface. The two branches of the GT1b polysaccharide, together with the protein receptor site, impose strict geometric constraints on the mode of interaction with the membrane surface and strongly support a model where one end of the 100 A long translocation domain helix bundle swing into contact with the membrane, initiating the membrane anchoring event.

Crystal structure of botulinum neurotoxin type A in complex with the cell surface co-receptor GT1b-insight into the toxin-neuron interaction.,Stenmark P, Dupuy J, Imamura A, Kiso M, Stevens RC PLoS Pathog. 2008 Aug 15;4(8):e1000129. PMID:18704164^[1]

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

References

↑ Stenmark P, Dupuy J, Imamura A, Kiso M, Stevens RC. Crystal structure of botulinum neurotoxin type A in complex with the cell surface co-receptor GT1b-insight into the toxin-neuron interaction. PLoS Pathog. 2008 Aug 15;4(8):e1000129. PMID:18704164 doi:10.1371/journal.ppat.1000129

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

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/2vu9"

Categories: Clostridium botulinum A | Large Structures | Dupuy J | Stenmark P | Stevens RC

@@ Line 1: / Line 1: @@
 ==CRYSTAL STRUCTURE OF BOTULINUM NEUROTOXIN SEROTYPE A BINDING DOMAIN IN COMPLEX WITH GT1B==
-<StructureSection load='2vu9' size='340' side='right' caption='[[2vu9]], [[Resolution|resolution]] 1.60&Aring;' scene=''>
+<StructureSection load='2vu9' size='340' side='right'caption='[[2vu9]], [[Resolution|resolution]] 1.60&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[2vu9]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Clostridium_botulinum_a Clostridium botulinum a]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2VU9 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2VU9 FirstGlance]. <br>
+<table><tr><td colspan='2'>[[2vu9]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Clostridium_botulinum_A Clostridium botulinum A]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2VU9 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2VU9 FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=BGC:BETA-D-GLUCOSE'>BGC</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=GAL:BETA-D-GALACTOSE'>GAL</scene>, <scene name='pdbligand=NGA:N-ACETYL-D-GALACTOSAMINE'>NGA</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]] 1.6&#8491;</td></tr>
-<tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=SIA:O-SIALIC+ACID'>SIA</scene></td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=BGC:BETA-D-GLUCOSE'>BGC</scene>, <scene name='pdbligand=GAL:BETA-D-GALACTOSE'>GAL</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=NGA:N-ACETYL-D-GALACTOSAMINE'>NGA</scene>, <scene name='pdbligand=SIA:O-SIALIC+ACID'>SIA</scene></td></tr>
-<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3bta|3bta]], [[2vua|2vua]], [[1uee|1uee]]</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=2vu9 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2vu9 OCA], [https://pdbe.org/2vu9 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2vu9 RCSB], [https://www.ebi.ac.uk/pdbsum/2vu9 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2vu9 ProSAT]</span></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=2vu9 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2vu9 OCA], [http://pdbe.org/2vu9 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2vu9 RCSB], [http://www.ebi.ac.uk/pdbsum/2vu9 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2vu9 ProSAT]</span></td></tr>
 </table>
+== Function ==
+[https://www.uniprot.org/uniprot/BXA1_CLOBH BXA1_CLOBH] 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 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.
 == Evolutionary Conservation ==
 [[Image:Consurf_key_small.gif|200px|right]]
 Check<jmol>
   <jmolCheckbox>
-    <scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/vu/2vu9_consurf.spt"</scriptWhenChecked>
+    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/vu/2vu9_consurf.spt"</scriptWhenChecked>
     <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
     <text>to colour the structure by Evolutionary Conservation</text>
@@ Line 31: / Line 31: @@
 ==See Also==
-*[[Botulinum neurotoxin|Botulinum neurotoxin]]
+*[[Botulinum neurotoxin 3D structures|Botulinum neurotoxin 3D structures]]
 == References ==
 <references/>
 __TOC__
 </StructureSection>
-[[Category: Bontoxilysin]]
+[[Category: Clostridium botulinum A]]
-[[Category: Clostridium botulinum a]]
+[[Category: Large Structures]]
-[[Category: Dupuy, J]]
+[[Category: Dupuy J]]
-[[Category: Stenmark, P]]
+[[Category: Stenmark P]]
-[[Category: Stevens, R C]]
+[[Category: Stevens RC]]
-[[Category: Ganglioside]]
-[[Category: Hydrolase]]
-[[Category: Membrane]]
-[[Category: Metal-binding]]
-[[Category: Metalloprotease]]
-[[Category: Neurotoxin]]
-[[Category: Protease]]
-[[Category: Receptor]]
-[[Category: Secreted]]
-[[Category: Toxin]]

2vu9

From Proteopedia

Current revision

CRYSTAL STRUCTURE OF BOTULINUM NEUROTOXIN SEROTYPE A BINDING DOMAIN IN COMPLEX WITH GT1B

Structural highlights

Function

Evolutionary Conservation

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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