| Structural highlights
Function
CA1A_CONER Alpha-conotoxins act on postsynaptic membranes, they bind to the nicotinic acetylcholine receptors (nAChR) and thus inhibit them. Probable competitive antagonist of fish muscle acetylcholine receptor (PubMed:32245200). Inhibits postsynaptic nicotinic acetylcholine receptors (nAChRs) from zebrafish (IC(50)=58-100 nM) (PubMed:32245200). Blocks mammalian nAChR composed of alpha-1/gamma and alpha-1/delta subunits. Blocks central nervous system nAChR composed of alpha-4-beta-2/CHRNA4-CHRNB2 subunits and peripheral nervous system nAChR composed of alpha-3-beta-4/CHRNA3-CHRNB4 subunits. Low toxin concentrations potentiate currents in muscle nAChR composed of alpha-1-beta-1-gamma-delta (CHRNA1-CHRNB1-CHRNG-CHRND) subunits and central nervous system nAChR composed of alpha-4-beta-2/CHRNA4-CHRNB2 subunits, but not peripheral nervous system nAChR composed of alpha-3-beta-4 subunits. Also exhibits inhibition of D.melanogaster alpha-7/CHRNA7 nAChRs (PubMed:25466886). Has possibly a distinct nAChR binding mode from other alpha-conotoxins, due to a different three residue motif (lacks the Ser-Xaa-Pro motif) (By similarity).[UniProtKB:Q2I2R8][1] [2] [3] [4]
Publication Abstract from PubMed
A high resolution structure of alpha-conotoxin EI has been determined by (1)H NMR spectroscopy and molecular modeling. alpha-Conotoxin EI has the same disulfide framework as alpha 4/7 conotoxins targeting neuronal nicotinic acetylcholine receptors but antagonizes the neuromuscular receptor as do the alpha 3/5 and alpha A conotoxins. The unique binding preference of alpha-conotoxin EI to the alpha(1)/delta subunit interface of Torpedo neuromuscular receptor makes it a valuable structural template for superposition of various alpha-conotoxins possessing distinct receptor subtype specificities. Structural comparison of alpha-conotoxin EI with the gamma-subunit favoring alpha-conotoxin GI suggests that the Torpedo delta-subunit preference of the former originates from its second loop. Superposition of three-dimensional structures of seven alpha-conotoxins reveals that the estimated size of the toxin-binding pocket in nicotinic acetylcholine receptor is approximately 20 A (height) x 20 A (width) x 15 A (thickness).
Solution conformation of alpha-conotoxin EI, a neuromuscular toxin specific for the alpha 1/delta subunit interface of torpedo nicotinic acetylcholine receptor.,Park KH, Suk JE, Jacobsen R, Gray WR, McIntosh JM, Han KH J Biol Chem. 2001 Dec 28;276(52):49028-33. Epub 2001 Oct 18. PMID:11641403[5]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Lopez-Vera E, Aguilar MB, Schiavon E, Marinzi C, Ortiz E, Restano Cassulini R, Batista CV, Possani LD, Heimer de la Cotera EP, Peri F, Becerril B, Wanke E. Novel alpha-conotoxins from Conus spurius and the alpha-conotoxin EI share high-affinity potentiation and low-affinity inhibition of nicotinic acetylcholine receptors. FEBS J. 2007 Aug;274(15):3972-85. Epub 2007 Jul 16. PMID:17635581 doi:http://dx.doi.org/10.1111/j.1742-4658.2007.05931.x
- ↑ Heghinian MD, Mejia M, Adams DJ, Godenschwege TA, Marí F. Inhibition of cholinergic pathways in Drosophila melanogaster by α-conotoxins. FASEB J. 2015 Mar;29(3):1011-8. PMID:25466886 doi:10.1096/fj.14-262733
- ↑ Rybin MJ, O'Brien H, Ramiro IBL, Azam L, McIntosh JM, Olivera BM, Safavi-Hemami H, Yoshikami D. αM-Conotoxin MIIIJ Blocks Nicotinic Acetylcholine Receptors at Neuromuscular Junctions of Frog and Fish. Toxins (Basel). 2020 Mar 21;12(3):197. PMID:32245200 doi:10.3390/toxins12030197
- ↑ Martinez JS, Olivera BM, Gray WR, Craig AG, Groebe DR, Abramson SN, McIntosh JM. alpha-Conotoxin EI, a new nicotinic acetylcholine receptor antagonist with novel selectivity. Biochemistry. 1995 Nov 7;34(44):14519-26. PMID:7578057
- ↑ Park KH, Suk JE, Jacobsen R, Gray WR, McIntosh JM, Han KH. Solution conformation of alpha-conotoxin EI, a neuromuscular toxin specific for the alpha 1/delta subunit interface of torpedo nicotinic acetylcholine receptor. J Biol Chem. 2001 Dec 28;276(52):49028-33. Epub 2001 Oct 18. PMID:11641403 doi:10.1074/jbc.M107798200
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