1ljz
From Proteopedia
(Difference between revisions)
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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== | ||
| - | <StructureSection load='1ljz' size='340' side='right'caption='[[1ljz | + | <StructureSection load='1ljz' size='340' side='right'caption='[[1ljz]]' scene=''> |
== Structural highlights == | == Structural highlights == | ||
| - | <table><tr><td colspan='2'>[[1ljz]] 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=1LJZ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1LJZ FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[1ljz]] 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=1LJZ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1LJZ FirstGlance]. <br> |
| - | </td></tr><tr id=' | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Solution NMR</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=1ljz FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1ljz OCA], [https://pdbe.org/1ljz PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1ljz RCSB], [https://www.ebi.ac.uk/pdbsum/1ljz PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1ljz ProSAT]</span></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=1ljz FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1ljz OCA], [https://pdbe.org/1ljz PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1ljz RCSB], [https://www.ebi.ac.uk/pdbsum/1ljz PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1ljz ProSAT]</span></td></tr> | ||
</table> | </table> | ||
== Function == | == Function == | ||
| - | + | [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=1ljz 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=1ljz ConSurf]. | ||
<div style="clear:both"></div> | <div style="clear:both"></div> | ||
| - | <div style="background-color:#fffaf0;"> | ||
| - | == Publication Abstract from PubMed == | ||
| - | 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®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| - | </div> | ||
| - | <div class="pdbe-citations 1ljz" 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]] | ||
| - | [[Category: Anglister | + | [[Category: Torpedo marmorata]] |
| - | [[Category: Chill | + | [[Category: Anglister J]] |
| - | [[Category: Eisenstein | + | [[Category: Chill JH]] |
| - | [[Category: Samson | + | [[Category: Eisenstein M]] |
| - | [[Category: Scherf | + | [[Category: Samson AO]] |
| - | + | [[Category: Scherf T]] | |
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Revision as of 08:10, 3 April 2024
NMR structure of an AChR-peptide (Torpedo Californica, alpha-subunit residues 182-202) in complex with alpha-Bungarotoxin
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