15 research outputs found
Chemical synthesis and characterization of maurocalcine, a scorpion toxin that activates Ca 2+ release channel/ryanodine receptors
International audienceMaurocalcine is a novel toxin isolated from the venom of the chactid scorpion Scorpio maurus palmatus. It is a 33âmer basic peptide crossâlinked by three disulfide bridges, which shares 82% sequence identity with imperatoxin A, a scorpion toxin from the venom of Pandinus imperator. Maurocalcine is peculiar in terms of structural properties since it does not possess any consensus motif reported so far in other scorpion toxins. Due to its low concentration in venom (0.5% of the proteins), maurocalcine was chemically synthesized by means of an optimized solidâphase method, and purified after folding/oxidation by using both C18 reversedâphase and ion exchange highâpressure liquid chromatographies. The synthetic product (sMCa) was characterized. The halfâcystine pairing pattern of sMCa was identified by enzymeâbased cleavage and Edman sequencing. The pairings were Cys3âCys17, Cys10âCys21, and Cys16âCys32. In vivo, the sMCa was lethal to mice following intracerebroventricular inoculation (LD50, 20 ÎŒg/mouse). In vitro, electrophysiological experiments based on recordings of single channels incorporated into planar lipid bilayers showed that sMCa potently and reversibly modifies channel gating behavior of the type 1 ryanodine receptor by inducing prominent subconductance behavior