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1lxg

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[[Image:1lxg.gif|left|200px]]
 
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==Solution structure of alpha-cobratoxin complexed with a cognate peptide (structure ensemble)==
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The line below this paragraph, containing "STRUCTURE_1lxg", creates the "Structure Box" on the page.
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<StructureSection load='1lxg' size='340' side='right'caption='[[1lxg]]' scene=''>
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You may change the PDB parameter (which sets the PDB file loaded into the applet)
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== Structural highlights ==
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or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
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<table><tr><td colspan='2'>[[1lxg]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Naja_kaouthia Naja kaouthia] and [https://en.wikipedia.org/wiki/Tetronarce_californica Tetronarce californica]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1LXG OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1LXG FirstGlance]. <br>
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or leave the SCENE parameter empty for the default display.
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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='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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{{STRUCTURE_1lxg| PDB=1lxg | SCENE= }}
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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=1lxg FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1lxg OCA], [https://pdbe.org/1lxg PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1lxg RCSB], [https://www.ebi.ac.uk/pdbsum/1lxg PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1lxg ProSAT]</span></td></tr>
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</table>
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'''Solution structure of alpha-cobratoxin complexed with a cognate peptide (structure ensemble)'''
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== Function ==
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[https://www.uniprot.org/uniprot/3L21_NAJKA 3L21_NAJKA] Monomer: binds with high affinity to muscular (alpha-1-beta-1-gamma-delta/CHRNA1-CHRNB1-CHRNG-CHRND) nAChR (tested on Torpedo californica, Kd=0.2-4.5 nM) and neuronal alpha-7/CHRNA7 nicotinic acetylcholine receptors (Kd=13-105 nM) (PubMed:18381281, PubMed:9305882, PubMed:22223648). Also inhibits GABA(A) channels (PubMed:26221036). Heteropentamer targets studied are composed of alpha-1-beta-3-gamma-2 (GABRA1-GABRB3-GABRG2) subunits (IC(50)=236 nM), alpha-1-beta-2-gamma-2 (GABRA1-GABRB2-GABRG2) subunits (IC(50)=469 nM), alpha-2-beta-2-gamma-2 (GABRA2-GABRB2-GABRG2) subunits (IC(50)=485 nM), alpha-5-beta-3-gamma-2 (GABRA5-GABRB3-GABRG2) subunits (IC(50)=635 nM), and alpha-2-beta-3-gamma-2 (GABRA2-GABRB3-GABRG2) subunits (IC(50)=1099 nM) (activated by 10 uM GABA) (PubMed:26221036).<ref>PMID:18381281</ref> <ref>PMID:22223648</ref> <ref>PMID:26221036</ref> <ref>PMID:30025921</ref> Homodimer: binds with high affinity (but lower than the monomeric form) to muscular (IC(50)=9.7 nM) and with low affinity to neuronal alpha-7/CHRNA7 nAChRs (IC(50)=1370 nM) (PubMed:22223648). However, it acquires (compared to the monomeric form) the capacity to block alpha-3/beta-2 (CHRNA3/CHRNB2) nAChRs (PubMed:18381281).<ref>PMID:18381281</ref> <ref>PMID:22223648</ref> Heterodimer with cytotoxin 3 (AC P01446): is slightly more active than the homodimer in inhibiting alpha-7/CHRNA7 nAChR and is considerably more active in blocking the alpha-3-beta-2/CHRNA3-CHRNB2 nAChR.<ref>PMID:22223648</ref>
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== Evolutionary Conservation ==
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==Overview==
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[[Image:Consurf_key_small.gif|200px|right]]
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The alpha18-mer peptide, spanning residues 181-198 of the Torpedo nicotinic acetylcholine receptor alpha1 subunit, contains key binding determinants for agonists and competitive antagonists. To investigate whether the alpha18-mer can bind other alpha-neurotoxins besides alpha-bungarotoxin, we designed a two-dimensional (1)H-(15)N heteronuclear single quantum correlation experiment to screen four related neurotoxins for their binding ability to the peptide. Of the four toxins tested (erabutoxin a, erabutoxin b, LSIII, and alpha-cobratoxin), only alpha-cobratoxin binds the alpha18-mer to form a 1:1 complex. The NMR solution structure of the alpha-cobratoxin.alpha18-mer complex was determined with a backbone root mean square deviation of 1.46 A. In the structure, alpha-cobratoxin contacts the alpha18-mer at the tips of loop I and II and through C-terminal cationic residues. The contact zone derived from the intermolecular nuclear Overhauser effects is in agreement with recent biochemical data. Furthermore, the structural models support the involvement of cation-pi interactions in stabilizing the complex. In addition, the binding screen results suggest that C-terminal cationic residues of alpha-bungarotoxin and alpha-cobratoxin contribute significantly to binding of the alpha18-mer. Finally, we present a structural model for nicotinic acetylcholine receptor-alpha-cobratoxin interaction by superimposing the alpha-cobratoxin.alpha18-mer complex onto the crystal structure of the acetylcholine-binding protein (Protein Data Bank code ).
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Check<jmol>
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<jmolCheckbox>
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==About this Structure==
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<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/lx/1lxg_consurf.spt"</scriptWhenChecked>
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1LXG is a [[Protein complex]] structure of sequences from [http://en.wikipedia.org/wiki/Naja_kaouthia Naja kaouthia] and [http://en.wikipedia.org/wiki/Torpedo_californica Torpedo californica]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1LXG OCA].
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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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==Reference==
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</jmolCheckbox>
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NMR-based binding screen and structural analysis of the complex formed between alpha-cobratoxin and an 18-mer cognate peptide derived from the alpha 1 subunit of the nicotinic acetylcholine receptor from Torpedo californica., Zeng H, Hawrot E, J Biol Chem. 2002 Oct 4;277(40):37439-45. Epub 2002 Jul 19. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/12133834 12133834]
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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=1lxg ConSurf].
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<div style="clear:both"></div>
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== References ==
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<references/>
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__TOC__
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</StructureSection>
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[[Category: Large Structures]]
[[Category: Naja kaouthia]]
[[Category: Naja kaouthia]]
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[[Category: Protein complex]]
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[[Category: Tetronarce californica]]
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[[Category: Torpedo californica]]
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[[Category: Hawrot E]]
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[[Category: Hawrot, E.]]
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[[Category: Zeng H]]
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[[Category: Zeng, H.]]
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[[Category: Alpha-cobratoxin]]
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[[Category: Nicotinic acetylcholine receptor]]
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[[Category: Protein-protein interaction]]
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[[Category: Toxin]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May 3 00:23:54 2008''
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Current revision

Solution structure of alpha-cobratoxin complexed with a cognate peptide (structure ensemble)

PDB ID 1lxg

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