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1kc4

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[[Image:1kc4.jpg|left|200px]]
 
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{{Structure
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==NMR Structural Analysis of the Complex Formed Between alpha-Bungarotoxin and the Principal alpha-Neurotoxin Binding Sequence on the alpha7 Subunit of a Neuronal Nicotinic Acetylcholine Receptor==
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|PDB= 1kc4 |SIZE=350|CAPTION= <scene name='initialview01'>1kc4</scene>
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<StructureSection load='1kc4' size='340' side='right'caption='[[1kc4]]' scene=''>
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|SITE=
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== Structural highlights ==
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|LIGAND= <scene name='pdbligand=HSL:HOMOSERINE+LACTONE'>HSL</scene>
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<table><tr><td colspan='2'>[[1kc4]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Bungarus_multicinctus Bungarus multicinctus] and [https://en.wikipedia.org/wiki/Gallus_gallus Gallus gallus]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1KC4 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1KC4 FirstGlance]. <br>
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|ACTIVITY=
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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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|GENE=
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<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=HSL:HOMOSERINE+LACTONE'>HSL</scene></td></tr>
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|DOMAIN=
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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=1kc4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1kc4 OCA], [https://pdbe.org/1kc4 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1kc4 RCSB], [https://www.ebi.ac.uk/pdbsum/1kc4 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1kc4 ProSAT]</span></td></tr>
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|RELATEDENTRY=[[1abt|1ABT]], [[1idh|1IDH]], [[2abx|2ABX]], [[1i9b|1I9B]], [[1haj|1HAJ]], [[1hc9|1HC9]], [[1bxp|1BXP]], [[1jbd|1JBD]], [[1ikc|1IKC]], [[1kfh|1KFH]], [[1kl8|1KL8]]
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</table>
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|RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1kc4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1kc4 OCA], [http://www.ebi.ac.uk/pdbsum/1kc4 PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=1kc4 RCSB]</span>
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== Function ==
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}}
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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>
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== Evolutionary Conservation ==
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[[Image:Consurf_key_small.gif|200px|right]]
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Check<jmol>
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<jmolCheckbox>
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<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/kc/1kc4_consurf.spt"</scriptWhenChecked>
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<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
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<text>to colour the structure by Evolutionary Conservation</text>
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</jmolCheckbox>
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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=1kc4 ConSurf].
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<div style="clear:both"></div>
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'''NMR Structural Analysis of the Complex Formed Between alpha-Bungarotoxin and the Principal alpha-Neurotoxin Binding Sequence on the alpha7 Subunit of a Neuronal Nicotinic Acetylcholine Receptor'''
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==See Also==
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*[[Bungarotoxin 3D structures|Bungarotoxin 3D structures]]
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== References ==
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==Overview==
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<references/>
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We report a new, higher resolution NMR structure of alpha-bungarotoxin that defines the structure-determining disulfide core and beta-sheet regions. We further report the NMR structure of the stoichiometric complex formed between alpha-bungarotoxin and a recombinantly expressed 19-mer peptide ((178)IPGKRTESFYECCKEPYPD(196)) derived from the alpha7 subunit of the chick neuronal nicotinic acetylcholine receptor. A comparison of these two structures reveals binding-induced stabilization of the flexible tip of finger II in alpha-bungarotoxin. The conformational rearrangements in the toxin create an extensive binding surface involving both sides of the alpha7 19-mer hairpin-like structure. At the contact zone, Ala(7), Ser(9), and Ile(11) in finger I and Arg(36), Lys(38), Val(39), and Val(40) in finger II of alpha-bungarotoxin interface with Phe(186), Tyr(187), Glu(188), and Tyr(194) in the alpha7 19-mer underscoring the importance of receptor aromatic residues as critical neurotoxin-binding determinants. Superimposing the structure of the complex onto that of the acetylcholine-binding protein (1I9B), a soluble homologue of the extracellular domain of the alpha7 receptor, places alpha-bungarotoxin at the peripheral surface of the inter-subunit interface occluding the agonist-binding site. The disulfide-rich core of alpha-bungarotoxin is suggested to be tilted in the direction of the membrane surface with finger II extending into the proposed ligand-binding cavity.
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__TOC__
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</StructureSection>
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==About this Structure==
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1KC4 is a [[Protein complex]] structure of sequences from [http://en.wikipedia.org/wiki/Bungarus_multicinctus Bungarus multicinctus] and [http://en.wikipedia.org/wiki/Gallus_gallus Gallus gallus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1KC4 OCA].
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==Reference==
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NMR structural analysis of alpha-bungarotoxin and its complex with the principal alpha-neurotoxin-binding sequence on the alpha 7 subunit of a neuronal nicotinic acetylcholine receptor., Moise L, Piserchio A, Basus VJ, Hawrot E, J Biol Chem. 2002 Apr 5;277(14):12406-17. Epub 2002 Jan 14. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/11790782 11790782]
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[[Category: Bungarus multicinctus]]
[[Category: Bungarus multicinctus]]
[[Category: Gallus gallus]]
[[Category: Gallus gallus]]
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[[Category: Protein complex]]
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[[Category: Large Structures]]
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[[Category: Basus, V J.]]
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[[Category: Basus VJ]]
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[[Category: Hawrot, E.]]
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[[Category: Hawrot E]]
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[[Category: Moise, L.]]
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[[Category: Moise L]]
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[[Category: Piserchio, A.]]
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[[Category: Piserchio A]]
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[[Category: alpha-bungarotoxin]]
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[[Category: alpha-neurotoxin]]
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[[Category: ligand-gated ion channel]]
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[[Category: nicotinic acetylcholine receptor alpha 7 subunit]]
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[[Category: nmr]]
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[[Category: protein-peptide complex]]
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[[Category: protein-protein interaction]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Mar 30 21:46:22 2008''
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Current revision

NMR Structural Analysis of the Complex Formed Between alpha-Bungarotoxin and the Principal alpha-Neurotoxin Binding Sequence on the alpha7 Subunit of a Neuronal Nicotinic Acetylcholine Receptor

PDB ID 1kc4

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