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.
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Research Article|
April 26 2007
Hemicalcin, a new toxin from the Iranian scorpion Hemiscorpius lepturus which is active on ryanodine-sensitive Ca2+ channels
Delavar Shahbazzadeh;
Delavar Shahbazzadeh
1
*Laboratoire des Venins et Toxines, Institut Pasteur de Tunis, 13 place Pasteur, Tunis, BP-74, 1002 Tunisia
†Biotechnology Department, Institute Pasteur of Iran, P.O. Box 13164, Tehran, Iran
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Najet Srairi-Abid;
*Laboratoire des Venins et Toxines, Institut Pasteur de Tunis, 13 place Pasteur, Tunis, BP-74, 1002 Tunisia
2To whom correspondence should be addressed (email najet.abid@pasteur.rns.tn).
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Wei Feng;
Wei Feng
‡Department of Veterinary Medicine-Molecular Biosciences and Center for Children's Environmental Health, University of California Davis, One Shields Avenue, Davis, CA 95616, U.S.A.
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Narendra Ram;
Narendra Ram
§INSERM U607, Canaux Calciques, Fonctions et Pathologies, Département Réponse et Dynamique Cellulaire, Commissariat à l'Energie Atomique, 17 rue des Martyrs, 38054 Grenoble Cedex 09, France
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Lamia Borchani;
Lamia Borchani
*Laboratoire des Venins et Toxines, Institut Pasteur de Tunis, 13 place Pasteur, Tunis, BP-74, 1002 Tunisia
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Michel Ronjat;
Michel Ronjat
§INSERM U607, Canaux Calciques, Fonctions et Pathologies, Département Réponse et Dynamique Cellulaire, Commissariat à l'Energie Atomique, 17 rue des Martyrs, 38054 Grenoble Cedex 09, France
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Abolfazl Akbari;
Abolfazl Akbari
∥Razi Vaccine & Serum Research Institute, 31975/148 Karaj, Iran
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Isaac N. Pessah;
Isaac N. Pessah
‡Department of Veterinary Medicine-Molecular Biosciences and Center for Children's Environmental Health, University of California Davis, One Shields Avenue, Davis, CA 95616, U.S.A.
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Michel De Waard;
Michel De Waard
§INSERM U607, Canaux Calciques, Fonctions et Pathologies, Département Réponse et Dynamique Cellulaire, Commissariat à l'Energie Atomique, 17 rue des Martyrs, 38054 Grenoble Cedex 09, France
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Mohamed El Ayeb
Mohamed El Ayeb
*Laboratoire des Venins et Toxines, Institut Pasteur de Tunis, 13 place Pasteur, Tunis, BP-74, 1002 Tunisia
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Publisher: Portland Press Ltd
Received:
September 12 2006
Revision Received:
January 24 2007
Accepted:
February 12 2007
Accepted Manuscript online:
February 12 2007
Online ISSN: 1470-8728
Print ISSN: 0264-6021
© 2007 Biochemical Society
2007
Biochem J (2007) 404 (1): 89–96.
Article history
Received:
September 12 2006
Revision Received:
January 24 2007
Accepted:
February 12 2007
Accepted Manuscript online:
February 12 2007
Citation
Delavar Shahbazzadeh, Najet Srairi-Abid, Wei Feng, Narendra Ram, Lamia Borchani, Michel Ronjat, Abolfazl Akbari, Isaac N. Pessah, Michel De Waard, Mohamed El Ayeb; Hemicalcin, a new toxin from the Iranian scorpion Hemiscorpius lepturus which is active on ryanodine-sensitive Ca2+ channels. Biochem J 15 May 2007; 404 (1): 89–96. doi: https://doi.org/10.1042/BJ20061404
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