title: Hemicalcin, a new toxin from the Iranian scorpion Hemiscorpius lepturus which is active on ryanodine-sensitive Ca2+ channels.
abstract: In the present work, we purified and characterized a novel toxin named hemicalcin from the venom of the Iranian chactoid scorpion Hemiscorpius lepturus where it represents 0.6% of the total protein content. It is a 33-mer basic peptide reticulated by three disulfide bridges, and that shares between 85 and 91% sequence identity with four other toxins, all known or supposed to be active on ryanodine-sensitive calcium channels. Hemicalcin differs from these other toxins by seven amino acids at positions 9 (leucine/arginine), 12 (alanine/glutamic acid), 13 (aspartic acid/asparagine), 14 (lysine/asparagine), 18 (serine/glycine), 26 (threonine/alanine) and 28 (proline/isoleucine/alanine). In spite of these differences, hemicalcin remains active on ryanodine-sensitive Ca2+ channels, since it increases [3H]ryanodine binding on RyR1 (ryanodine receptor type 1) and triggers Ca2+ release from sarcoplasmic vesicles. Bilayer lipid membrane experiments, in which the RyR1 channel is reconstituted and its gating properties are analysed, indicate that hemicalcin promotes an increase in the opening probability at intermediate concentration and induces a long-lasting subconductance level of 38% of the original amplitude at higher concentrations. Mice intracerebroventricular inoculation of 300 ng of hemicalcin induces neurotoxic symptoms in vivo, followed by death. Overall, these data identify a new biologically active toxin that belongs to a family of peptides active on the ryanodine-sensitive channel.
authors.affiliation: Laboratoire des Venins et Toxines, Institut Pasteur de Tunis, 13 place Pasteur, Tunis, BP-74, 1002 Tunisia.
authors.forename: Delavar
authors.initials: D
authors.lastname: Shahbazzadeh
authors.forename: Najet
authors.initials: N
authors.lastname: Srairi-Abid
authors.forename: Wei
authors.initials: W
authors.lastname: Feng
authors.forename: Narendra
authors.initials: N
authors.lastname: Ram
authors.forename: Lamia
authors.initials: L
authors.lastname: Borchani
authors.forename: Michel
authors.initials: M
authors.lastname: Ronjat
authors.forename: Abolfazl
authors.initials: A
authors.lastname: Akbari
authors.forename: Isaac N
authors.initials: IN
authors.lastname: Pessah
authors.forename: Michel
authors.initials: M
authors.lastname: De Waard
authors.forename: Mohamed
authors.initials: M
authors.lastname: El Ayeb
mesh_terms: D000818:Animals; D007492:Iran; D007928:Lethal Dose 50; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D012433:Ryanodine / Q000378:metabolism; D019837:Ryanodine Receptor Calcium Release Channel / Q000187:drug effects / Q000502:physiology*; D012604:Scorpion Venoms / Q000302:isolation & purification / Q000633:toxicity*; D012605:Scorpions
chemical_list: D019837:Ryanodine Receptor Calcium Release Channel; D012604:Scorpion Venoms; C519687:hemicalcin protein, Hemiscorpius lepturus; D012433:Ryanodine