A new fold in the scorpion toxin family, associated with an activity on a ryanodine-sensitive calcium channel

We determined the structure in solution by H-1 two-dimensional NMR of Mauro calcine from the venom of Scorpio maurus, This toxin has been demonstrated to be a potent effector of ryanodyne-sensitive calcium channel from skeleta l muscles. This is the first description of a scorpion toxin which folds fo llowing the Inhibitor Cystine Knot fold (ICK) already described for numerou s toxic and inhibitory peptides, as well as for various protease inhibitors , Its three dimensional structure consists of a compact disulfide-bonded co re from which emerge loops and the N-terminus, A double-stranded antiparall el beta-sheet comprises residues 20-23 and 30-33, A third extended strand ( residues 9-11) is perpendicular to the beta-sheet. Maurocalcine structure m imics the activating segment of the dihydropyridine receptor II-III loop an d is therefore potentially useful for dihydropyridine receptor/ ryanodine r eceptor interaction studies. Proteins 2000;40:436-442. (C) 2000 Wiley-Liss, Inc.