title: A chimeric scorpion alpha-toxin displays de novo electrophysiological properties similar to those of alpha-like toxins.
abstract: BotXIV and LqhalphaIT are two structurally related long chain scorpion alpha-toxins that inhibit sodium current inactivation in excitable cells. However, while LqhalphaIT from Leiurus quinquestriatus hebraeus is classified as a true and strong insect alpha-toxin, BotXIV from Buthus occitanus tunetanus is characterized by moderate biological activities. To assess the possibility that structural differences between these two molecules could reflect the localization of particular functional topographies, we compared their sequences. Three structurally deviating segments located in three distinct and exposed loops were identified. They correspond to residues 8-10, 19-22, and 38-43. To evaluate their functional role, three BotXIV/LqhalphaIT chimeras were designed by transferring the corresponding LqhalphaIT sequences into BotXIV. Structural and antigenic characterizations of the resulting recombinant chimera show that BotXIV can accommodate the imposed modifications, confirming the structural flexibility of that particular alpha/beta fold. Interestingly, substitution of residues 8-10 yields to a new electrophysiological profile of the corresponding variant, partially comparable to that one of alpha-like scorpion toxins. Taken together, these results suggest that even limited structural deviations can reflect functional diversity, and also that the structure-function relationships between insect alpha-toxins and alpha-like scorpion toxins are probably more complex than expected.
authors.affiliation: Laboratoire des Venins et Toxines, Institut Pasteur de Tunis, Tunisia. balkiss.bouhaoulala@pasteur.rns.tn
authors.forename: Balkiss
authors.initials: B
authors.lastname: Bouhaouala-Zahar
authors.forename: Rym
authors.initials: R
authors.lastname: Benkhalifa
authors.forename: Najet
authors.initials: N
authors.lastname: Srairi
authors.forename: Ilhem
authors.initials: I
authors.lastname: Zenouaki
authors.forename: Caroline
authors.initials: C
authors.lastname: Ligny-Lemaire
authors.forename: Pascal
authors.initials: P
authors.lastname: Drevet
authors.forename: François
authors.initials: F
authors.lastname: Sampieri
authors.forename: Marcel
authors.initials: M
authors.lastname: Pelhate
authors.forename: Mohamed
authors.initials: M
authors.lastname: El Ayeb
authors.forename: André
authors.initials: A
authors.lastname: Ménez
authors.forename: Habib
authors.initials: H
authors.lastname: Karoui
authors.forename: Frédéric
authors.initials: F
authors.lastname: Ducancel
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D004594:Electrophysiology; D000922:Immunotoxins / Q000737:chemistry* / Q000235:genetics / Q000276:immunology; D007313:Insecta; D051379:Mice; D008810:Mice, Inbred C57BL; D008958:Models, Molecular; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000302:isolation & purification; D012604:Scorpion Venoms / Q000737:chemistry* / Q000235:genetics / Q000276:immunology; D055672:Static Electricity; D018675:Toxicity Tests
chemical_list: C100683:Bot XIV toxin; D000922:Immunotoxins; C065190:LqhalphaIT toxin; D011994:Recombinant Proteins; D012604:Scorpion Venoms