1l4w

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==NMR structure of an AChR-peptide (Torpedo Californica, alpha-subunit residues 182-202) in complex with alpha-Bungarotoxin==
==NMR structure of an AChR-peptide (Torpedo Californica, alpha-subunit residues 182-202) in complex with alpha-Bungarotoxin==
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<StructureSection load='1l4w' size='340' side='right'caption='[[1l4w]], [[NMR_Ensembles_of_Models | 1 NMR models]]' scene=''>
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<StructureSection load='1l4w' size='340' side='right'caption='[[1l4w]]' scene=''>
== Structural highlights ==
== Structural highlights ==
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<table><tr><td colspan='2'>[[1l4w]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Bungarus_multicinctus Bungarus multicinctus]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1L4W OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1L4W FirstGlance]. <br>
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<table><tr><td colspan='2'>[[1l4w]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Bungarus_multicinctus Bungarus multicinctus] and [https://en.wikipedia.org/wiki/Torpedo_marmorata Torpedo marmorata]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1L4W OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1L4W FirstGlance]. <br>
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</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=1l4w FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1l4w OCA], [https://pdbe.org/1l4w PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1l4w RCSB], [https://www.ebi.ac.uk/pdbsum/1l4w PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1l4w ProSAT]</span></td></tr>
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Solution NMR</td></tr>
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1l4w FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1l4w OCA], [https://pdbe.org/1l4w PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1l4w RCSB], [https://www.ebi.ac.uk/pdbsum/1l4w PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1l4w ProSAT]</span></td></tr>
</table>
</table>
== Function ==
== Function ==
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[[https://www.uniprot.org/uniprot/NXL1A_BUNMU NXL1A_BUNMU]] Binds with high affinity to muscular and neuronal (alpha-7, alpha-8, and alpha-9) nicotinic acetylcholine receptors. Produces peripheral paralysis by blocking neuromuscular transmission at the postsynaptic site. Blocks the extracellular increase of dopamine evoked by nicotine only at the higher dose (4.2 uM).<ref>PMID:9305882</ref> <ref>PMID:9840221</ref> [[https://www.uniprot.org/uniprot/ACHA_TORMA ACHA_TORMA]] After binding acetylcholine, the AChR responds by an extensive change in conformation that affects all subunits and leads to opening of an ion-conducting channel across the plasma membrane.
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[https://www.uniprot.org/uniprot/3L21A_BUNMU 3L21A_BUNMU] Binds with high affinity to muscular (tested on Torpedo marmorata, Kd=0.4 nM) and neuronal (tested on chimeric alpha-7/CHRNA7, Kd=0.95 nM) nicotinic acetylcholine receptor (nAChR) and inhibits acetylcholine from binding to the receptor, thereby impairing neuromuscular and neuronal transmission (PubMed:9305882). It also shows an activity on GABA(A) receptors (PubMed:16549768, PubMed:25634239). It antagonises GABA-activated currents with high potency when tested on primary hippocampal neurons (PubMed:25634239). It inhibits recombinantly expressed GABA(A) receptors composed of alpha-2-beta-2-gamma-2 (GABRA2-GABRB2-GABRG2) subunits with high potency (62.3% inhibition at 20 uM of toxin) (PubMed:25634239). It also shows a weaker inhibition on GABA(A) receptors composed of alpha-1-beta-2-gamma-2 (GABRA1-GABRB2-GABRG2) subunits, alpha-4-beta-2-gamma-2 (GABRA4-GABRB2-GABRG2) subunits, and alpha-5-beta-2-gamma-2 (GABRA5-GABRB2-GABRG2) subunits (PubMed:25634239). A very weak inhibition is also observed on GABA(A) receptor composed of alpha-1-beta-3-gamma-2 (GABRA1-GABRB3-GABRG2) (PubMed:26221036). It has also been shown to bind and inhibit recombinant GABA(A) receptor beta-3/GABRB3 subunit (Kd=about 50 nM) (PubMed:16549768). In addition, it blocks the extracellular increase of dopamine evoked by nicotine only at the higher dose (4.2 uM) (PubMed:9840221).<ref>PMID:16549768</ref> <ref>PMID:25634239</ref> <ref>PMID:9305882</ref> <ref>PMID:9840221</ref>
== Evolutionary Conservation ==
== Evolutionary Conservation ==
[[Image:Consurf_key_small.gif|200px|right]]
[[Image:Consurf_key_small.gif|200px|right]]
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</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=1l4w ConSurf].
</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=1l4w ConSurf].
<div style="clear:both"></div>
<div style="clear:both"></div>
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<div style="background-color:#fffaf0;">
 
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== Publication Abstract from PubMed ==
 
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The structure of a peptide corresponding to residues 182-202 of the acetylcholine receptor alpha1 subunit in complex with alpha-bungarotoxin was solved using NMR spectroscopy. The peptide contains the complete sequence of the major determinant of AChR involved in alpha-bungarotoxin binding. One face of the long beta hairpin formed by the AChR peptide consists of exposed nonconserved residues, which interact extensively with the toxin. Mutations of these receptor residues confer resistance to the toxin. Conserved AChR residues form the opposite face of the beta hairpin, which creates the inner and partially hidden pocket for acetylcholine. An NMR-derived model for the receptor complex with two alpha-bungarotoxin molecules shows that this pocket is occupied by the conserved alpha-neurotoxin residue R36, which forms cation-pi interactions with both alphaW149 and gammaW55/deltaW57 of the receptor and mimics acetylcholine.
 
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The mechanism for acetylcholine receptor inhibition by alpha-neurotoxins and species-specific resistance to alpha-bungarotoxin revealed by NMR.,Samson A, Scherf T, Eisenstein M, Chill J, Anglister J Neuron. 2002 Jul 18;35(2):319-32. PMID:12160749<ref>PMID:12160749</ref>
 
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
 
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</div>
 
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<div class="pdbe-citations 1l4w" style="background-color:#fffaf0;"></div>
 
==See Also==
==See Also==
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[[Category: Bungarus multicinctus]]
[[Category: Bungarus multicinctus]]
[[Category: Large Structures]]
[[Category: Large Structures]]
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[[Category: Anglister, J]]
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[[Category: Torpedo marmorata]]
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[[Category: Eisenstein, M]]
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[[Category: Anglister J]]
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[[Category: Rodriguez, E]]
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[[Category: Eisenstein M]]
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[[Category: Samson, A O]]
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[[Category: Rodriguez E]]
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[[Category: Scherf, T]]
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[[Category: Samson AO]]
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[[Category: Acetylcholine receptor]]
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[[Category: Scherf T]]
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[[Category: Bungarotoxin]]
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[[Category: Intermolecular beta sheet]]
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[[Category: Protein-protein complex]]
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[[Category: Receptor]]
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[[Category: Toxin]]
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Revision as of 08:06, 3 April 2024

NMR structure of an AChR-peptide (Torpedo Californica, alpha-subunit residues 182-202) in complex with alpha-Bungarotoxin

PDB ID 1l4w

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