title: Maurotoxin, a four disulfide bridges scorpion toxin acting on K+ channels.
abstract: Maurotoxin, a toxin from the venom of the Tunisian chactoid scorpion Scorpio maurus, has been purified to homogeneity by gel filtration/reversed-phase HPLC, and characterized. It is a basic and C-terminal amidated 34-residue polypeptide cross-linked by four disulfide bridges. From Edman sequencing results, only six different pairings between the first six half-cystines were retained whereas a disulfide bridge was predicted between the two half-cystines in positions 31 and 34. Modelling based on the structure of charybdotoxin favored two different pairings, one of which possessed two disulfides in common with the general motif of scorpion toxins. The solid-phase technique was used to obtain synthetic maurotoxin, sMTX. The half-cystine pairings of sMTX were determined by enzymatic cleavage and were found to be Cys3 Cys24, Cys9-Cys29, Cys13-Cys19, and Cys31-34, in agreement with experimental data obtained with natural maurotoxin. Both natural and synthetic maurotoxins were lethal to mice following intracerebroventricular injection (LD50, 80 ng/mouse). They blocked the Kv1.1, Kv1.2, and Kv1.3 channels expressed in Xenopus oocytes with almost identical half-effects (IC50) in the range of 40, 0.8 and 150 nM, respectively. They also competed with 125I-apamin (SKca channel blocker) and 125I-kaliotoxin (Kv channel blocker) for binding to rat brain synaptosomes with IC50 of about 5 and 0.03 nM. As the natural and synthetic maurotoxins exhibit indistinguishable physicochemical and pharmacological properties, they are likely to adopt the same half-cystine pairing pattern which is unique among known scorpion toxins. However, this disulfide organization is different from those reported for Pandinus imperator and Heterometrus spinnifer toxins 1 (Pi1 and HsTx1), two novel four-disulfide bridged K+ channel-acting scorpion toxin sharing about 50-70% sequence identity with maurotoxin.
authors.affiliation: UMR 6560, Laboratoire de Biochimie-Ingénierie des Protéines, Marseille, France.
authors.forename: H
authors.initials: H
authors.lastname: Rochat
authors.forename: R
authors.initials: R
authors.lastname: Kharrat
authors.forename: J M
authors.initials: JM
authors.lastname: Sabatier
authors.forename: P
authors.initials: P
authors.lastname: Mansuelle
authors.forename: M
authors.initials: M
authors.lastname: Crest
authors.forename: M F
authors.initials: MF
authors.lastname: Martin-Eauclaire
authors.forename: F
authors.initials: F
authors.lastname: Sampieri
authors.forename: R
authors.initials: R
authors.lastname: Oughideni
authors.forename: K
authors.initials: K
authors.lastname: Mabrouk
authors.forename: G
authors.initials: G
authors.lastname: Jacquet
authors.forename: J
authors.initials: J
authors.lastname: Van Rietschoten
authors.forename: M
authors.initials: M
authors.lastname: El Ayeb
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D004220:Disulfides / Q000737:chemistry*; D007928:Lethal Dose 50; D051379:Mice; D008969:Molecular Sequence Data; D026902:Potassium Channel Blockers; D011487:Protein Conformation; D051381:Rats; D012604:Scorpion Venoms / Q000737:chemistry* / Q000633:toxicity; D012605:Scorpions; D017421:Sequence Analysis; D014981:Xenopus
chemical_list: D004220:Disulfides; D026902:Potassium Channel Blockers; D012604:Scorpion Venoms; C104498:maurotoxin