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| | ==NMR SOLUTION STRUCTURE OF ALPHA-CONOTOXIN IM1, 20 STRUCTURES== | | ==NMR SOLUTION STRUCTURE OF ALPHA-CONOTOXIN IM1, 20 STRUCTURES== |
| - | <StructureSection load='1im1' size='340' side='right' caption='[[1im1]], [[NMR_Ensembles_of_Models | 20 NMR models]]' scene=''> | + | <StructureSection load='1im1' size='340' side='right'caption='[[1im1]]' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[1im1]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Conim Conim]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1IM1 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1IM1 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[1im1]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Conus_imperialis Conus imperialis]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1IM1 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1IM1 FirstGlance]. <br> |
| - | </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=1im1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1im1 OCA], [http://pdbe.org/1im1 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1im1 RCSB], [http://www.ebi.ac.uk/pdbsum/1im1 PDBsum]</span></td></tr> | + | </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=1im1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1im1 OCA], [https://pdbe.org/1im1 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1im1 RCSB], [https://www.ebi.ac.uk/pdbsum/1im1 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1im1 ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/CA1_CONIM CA1_CONIM]] Alpha-conotoxins act on postsynaptic membranes, they bind to the nicotinic acetylcholine receptors (nAChR) and thus inhibit them. This toxin blocks mammalian neuronal nAChRs (alpha-3/beta-2 > alpha-7 > alpha-3/beta-4). Has no effect on nAChRs composed of alpha-2/beta-2, alpha-3/beta-2, alpha-4/beta-2, alpha-2/beta-4, alpha-3/beta-4, or alpha-4/beta-4 subunits. Acts voltage-independently. Is highly active against the neuromuscular receptor in frog.<ref>PMID:8206995</ref> | + | [https://www.uniprot.org/uniprot/CA1_CONIM CA1_CONIM] Alpha-conotoxins act on postsynaptic membranes, they bind to the nicotinic acetylcholine receptors (nAChR) and thus inhibit them. This toxin blocks mammalian neuronal nAChRs (alpha-3/beta-2 > alpha-7 > alpha-3/beta-4). Has no effect on nAChRs composed of alpha-2/beta-2, alpha-3/beta-2, alpha-4/beta-2, alpha-2/beta-4, alpha-3/beta-4, or alpha-4/beta-4 subunits. Acts voltage-independently. Is highly active against the neuromuscular receptor in frog.<ref>PMID:8206995</ref> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Conim]] | + | [[Category: Conus imperialis]] |
| - | [[Category: Luginbuhl, P]] | + | [[Category: Large Structures]] |
| - | [[Category: Mccabe, R T]] | + | [[Category: Luginbuhl P]] |
| - | [[Category: Rogers, J P]]
| + | [[Category: Mccabe RT]] |
| - | [[Category: Shen, G S]] | + | [[Category: Rogers JP]] |
| - | [[Category: Stevens, R C]] | + | [[Category: Shen GS]] |
| - | [[Category: Wemmer, D E]] | + | [[Category: Stevens RC]] |
| - | [[Category: Alpha-conotoxin]] | + | [[Category: Wemmer DE]] |
| - | [[Category: Neurotoxin]] | + | |
| - | [[Category: Nicotinic acetylcholine receptor antagonist]]
| + | |
| - | [[Category: Peptide toxin]]
| + | |
| Structural highlights
Function
CA1_CONIM Alpha-conotoxins act on postsynaptic membranes, they bind to the nicotinic acetylcholine receptors (nAChR) and thus inhibit them. This toxin blocks mammalian neuronal nAChRs (alpha-3/beta-2 > alpha-7 > alpha-3/beta-4). Has no effect on nAChRs composed of alpha-2/beta-2, alpha-3/beta-2, alpha-4/beta-2, alpha-2/beta-4, alpha-3/beta-4, or alpha-4/beta-4 subunits. Acts voltage-independently. Is highly active against the neuromuscular receptor in frog.[1]
Publication Abstract from PubMed
Alpha-Conotoxins, peptides produced by predatory species of Conus marine snails, are potent antagonists of nicotinic acetylcholine receptors (nAChRs), ligand-gated ion channels involved in synaptic transmission. We determined the NMR solution structure of the smallest known alpha-conotoxin, ImI, a 12 amino acid peptide that binds specifically to neuronal alpha7-containing nAChRs in mammals. Calculation of the structure was based on a total of 80 upper distance constraints and 31 dihedral angle constraints resulting in 20 representative conformers with an average pairwise rmsd of 0.44 A from the mean structure for the backbone atoms N, Calpha, and C' of residues 2-11. The structure of ImI is characterized by two compact loops, defined by two disulfide bridges, which form distinct subdomains separated by a deep cleft. Two short 310-helical regions in the first loop are followed by a C-terminal beta-turn in the second. The two disulfide bridges and Ala 9 form a rigid hydrophobic core, orienting the other amino acid side chains toward the surface. Comparison of the three-dimensional structure of ImI to those of the larger, 16 amino acid alpha-conotoxins PnIA, PnIB, MII, and EpI-also specific for neuronal nAChRs-reveals remarkable similarity in local backbone conformations and relative solvent-accessible surface areas. The core scaffold is conserved in all five conotoxins, whereas the residues in solvent-exposed positions are highly variable. The second helical region, and the specific amino acids that the helix exposes to solvent, may be particularly important for binding and selectivity. This comparative analysis provides a three-dimensional structural basis for interpretation of mutagenesis data and structure-activity relationships for ImI as well other neuronal alpha-conotoxins.
NMR solution structure of alpha-conotoxin ImI and comparison to other conotoxins specific for neuronal nicotinic acetylcholine receptors.,Rogers JP, Luginbuhl P, Shen GS, McCabe RT, Stevens RC, Wemmer DE Biochemistry. 1999 Mar 30;38(13):3874-82. PMID:10194298[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ McIntosh JM, Yoshikami D, Mahe E, Nielsen DB, Rivier JE, Gray WR, Olivera BM. A nicotinic acetylcholine receptor ligand of unique specificity, alpha-conotoxin ImI. J Biol Chem. 1994 Jun 17;269(24):16733-9. PMID:8206995
- ↑ Rogers JP, Luginbuhl P, Shen GS, McCabe RT, Stevens RC, Wemmer DE. NMR solution structure of alpha-conotoxin ImI and comparison to other conotoxins specific for neuronal nicotinic acetylcholine receptors. Biochemistry. 1999 Mar 30;38(13):3874-82. PMID:10194298 doi:10.1021/bi9826254
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