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

authors

• Mosbah Amor
• Kharrat Riadh
• Fajloun Ziad
• Renisio Jean-Guillaume
• Blanc Eric
• Sabatier Jean-Marc
• Ayeb Mohamed El
• Darbon Herve

keywords

• Scorpion toxin
• Dihydropyridine receptor
• Ryanodine receptor
• Maurocalcine
• Inhibitor‐cystine‐knot

abstract

We determined the structure in solution by 1H two‐dimensional NMR of Maurocalcine from the venom of Scorpio maurus. This toxin has been demonstrated to be a potent effector of ryanodyne‐sensitive calcium channel from skeletal muscles. This is the first description of a scorpion toxin which folds following the Inhibitor Cystine Knot fold (ICK) already described for numerous toxic and inhibitory peptides, as well as for various protease inhibitors. Its three dimensional structure consists of a compact disulfide‐bonded core from which emerge loops and the N‐terminus. A double‐stranded antiparallel β‐sheet comprises residues 20–23 and 30–33. A third extended strand (residues 9–11) is perpendicular to the β‐sheet. Maurocalcine structure mimics the activating segment of the dihydropyridine receptor II‐III loop and is therefore potentially useful for dihydropyridine receptor/ryanodine receptor interaction studies.

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