Solution Conformation of - Conotoxin EI , a Neuromuscular Toxin Specific for the 1 / Subunit Interface of Torpedo Nicotinic Acetylcholine Receptor

A high resolution structure of -conotoxin EI has been determined by H NMR spectroscopy and molecular modeling. -Conotoxin EI has the same disulfide framework as 4/7 conotoxins targeting neuronal nicotinic acetylcholine receptors but antagonizes the neuromuscular receptor as do the 3/5 and A conotoxins. The unique binding preference of -conotoxin EI to the 1/ subunit interface of Torpedo neuromuscular receptor makes it a valuable structural template for superposition of various -conotoxins possessing distinct receptor subtype specificities. Structural comparison of -conotoxin EI with the -subunit favoring -conotoxin GI suggests that the Torpedo -subunit preference of the former originates from its second loop. Superposition of three-dimensional structures of seven -conotoxins reveals that the estimated size of the toxin-binding pocket in nicotinic acetylcholine receptor is 20 Å (height) 20 Å (width) 15 Å (thickness).