title: Characterization of toxin III of the scorpion Leiurus quinquestriatus quinquestriatus: a new type of alpha-toxin highly toxic both to mammals and insects.
abstract: The primary structure of toxin III of Leiurus quinquestriatus quinquestriatus (Lqq III) was elucidated by automatic Edman degradation of the reduced and S-carboxymethylated protein and derived tryptic peptides. Like other scorpion toxins that are active on sodium channels, Lqq III, consisting of 64 amino acids, is a 7 kDa single-chain polypeptide crosslinked by four disulfide bridges. It belongs to the alpha-toxin group, as judged by competition experiments with 125I AaH II for binding to rat brain synaptosomes (K0.5 = 7 x 10(-7) M). Lqq III is the first alpha-toxin to be characterized that is highly toxic to mice [LD50 = 50 micrograms (7.1 nmol)/kg body wt], by subcutaneous injection, insects Blatella germanica [LD50 = 60 ng (8.5 pmol)/g body wt.] and Musca domestica [LD50 = 120 ng (17 pmol)/g body wt]. When tested via the intracerebroventricular route, the toxicity for mice [55 micrograms (8 nmol)/kg] was of the same order as that found by subcutaneous injection, indicating that Lqq III has a higher affinity for peripheral sodium channels that for those of the central nervous system. There are three differences between the sequences of Lqq III and Lqh alpha IT, an alpha-toxin isolated from the venom of Leiurus quinquestriatus hebraeus. These substitutions are found at positions 20, 24, and 64 (Ser-->Ala,Asp-->Glu and His-->Arg, respectively). Surprisingly Lqh alpha IT is only weakly active in mice [LD50 = 5 mg (0.7 mumol)/kg], while in insects its toxicity is similar to that of Lqq III [140 ng (20 pmol)/g body wt blowfly larvae]. These observations are relevant to the definition of scorpion toxin structure-activity relationships.
authors.affiliation: Laboratoire de Biochime, Centre National de la Recherche Scientifique URA 1455, Faculté de Médecine, Secteur Nord, Marseille, France.
authors.forename: C
authors.initials: C
authors.lastname: Kopeyan
authors.forename: P
authors.initials: P
authors.lastname: Mansuelle
authors.forename: M F
authors.initials: MF
authors.lastname: Martin-Eauclaire
authors.forename: H
authors.initials: H
authors.lastname: Rochat
authors.forename: F
authors.initials: F
authors.lastname: Miranda
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D003058:Cockroaches; D036341:Intercellular Signaling Peptides and Proteins; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D009498:Neurotoxins / Q000737:chemistry / Q000302:isolation & purification / Q000633:toxicity*; D010455:Peptides / Q000737:chemistry / Q000302:isolation & purification / Q000633:toxicity*; D012604:Scorpion Venoms / Q000737:chemistry / Q000302:isolation & purification / Q000633:toxicity*; D013329:Structure-Activity Relationship
chemical_list: D036341:Intercellular Signaling Peptides and Proteins; D009498:Neurotoxins; D010455:Peptides; D012604:Scorpion Venoms; C077585:leiurutoxin III