1k64
From Proteopedia
NMR Structue of alpha-conotoxin EI
Structural highlights
Function[CA1_CONER] Alpha-conotoxins act on postsynaptic membranes, they bind to the nicotinic acetylcholine receptors (nAChR) and thus inhibit them. Blocks mammalian nAChR composed of alpha-1/gamma and alpha-1/delta subunits. Blocks central nervous system nAChR composed of alpha-4/beta-2 subunits and peripheral nervous system nAChR composed of alpha-3/beta-4 subunits. Low toxin concentrations potentiate currents in muscle nAChR composed of alpha-1/beta-1/gamma/delta subunits and central nervous system nAChR composed of alpha-4/beta-2 subunits, but not peripheral nervous system nAChR composed of alpha-3/beta-4 subunits.[1] [2] Publication Abstract from PubMedA 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[3] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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