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New page: left|200px<br /><applet load="1im1" size="450" color="white" frame="true" align="right" spinBox="true" caption="1im1" /> '''NMR SOLUTION STRUCTURE OF ALPHA-CONOTOXIN IM...
 
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[[Image:1im1.jpg|left|200px]]<br /><applet load="1im1" size="450" color="white" frame="true" align="right" spinBox="true"
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'''NMR SOLUTION STRUCTURE OF ALPHA-CONOTOXIN IM1, 20 STRUCTURES'''<br />


==Overview==
==NMR SOLUTION STRUCTURE OF ALPHA-CONOTOXIN IM1, 20 STRUCTURES==
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.
<StructureSection load='1im1' size='340' side='right'caption='[[1im1]]' scene=''>
== Structural highlights ==
<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='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Solution NMR, 20 models</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>
== Function ==
[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;">
== 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.


==About this Structure==
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<ref>PMID:10194298</ref>
1IM1 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Conus_imperialis Conus imperialis]. Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1IM1 OCA].


==Reference==
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=10194298 10194298]
</div>
<div class="pdbe-citations 1im1" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Conus imperialis]]
[[Category: Conus imperialis]]
[[Category: Single protein]]
[[Category: Large Structures]]
[[Category: Luginbuhl, P.]]
[[Category: Luginbuhl P]]
[[Category: Mccabe, R.T.]]
[[Category: Mccabe RT]]
[[Category: Rogers, J.P.]]
[[Category: Rogers JP]]
[[Category: Shen, G.S.]]
[[Category: Shen GS]]
[[Category: Stevens, R.C.]]
[[Category: Stevens RC]]
[[Category: Wemmer, D.E.]]
[[Category: Wemmer DE]]
[[Category: alpha-conotoxin]]
[[Category: neurotoxin]]
[[Category: nicotinic acetylcholine receptor antagonist]]
[[Category: nmr structure]]
[[Category: peptide toxin]]
 
''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Tue Nov 20 17:29:48 2007''

Latest revision as of 10:27, 23 October 2024

NMR SOLUTION STRUCTURE OF ALPHA-CONOTOXIN IM1, 20 STRUCTURESNMR SOLUTION STRUCTURE OF ALPHA-CONOTOXIN IM1, 20 STRUCTURES

Structural highlights

1im1 is a 1 chain structure with sequence from Conus imperialis. Full experimental information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:Solution NMR, 20 models
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

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

  1. ↑ 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
  2. ↑ 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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