Maurotoxin, a four disulfide bridge toxin from Scorpio maurus venom: purification, structure and action on potassium channels.
A new toxin acting on K+ channels, maurotoxin (MTX), has been purified to homogeneity from the venom of the chactoid scorpion Scorpio maurus. MTX is a basic single chain 34 amino acid residue polypeptide, amidated at its C terminal, and crosslinked by four disulfide bridges. It shows 29-68% sequence identity with other K+ channel toxins, and presents an original disulfide pattern, the last two half-cystine residues (31-34) being connected. Although the first three disulfide bonds have not been defined experimentally, modelling based on the structure of charybdotoxin favored two combinations out of six, one of which has two bridges (3-24 and 9-29) in common with the general motif of scorpion toxins. The last bridge would connect residues 13 and 19. MTX inhibits the binding to rat brain synaptosomal membranes of both [125I]apamin, a SK(Ca) channel blocker (IC50 5 nM), and [125I]kaliotoxin, a Kv channel blocker (IC50 30 pM). MTX blocks the Kv1.1, Kv1.2 and Kv1.3 currents expressed in Xenopus oocytes with IC50 of 45, 0.8 and 180 nM, respectively. MTX represents a member of a new class of short toxins with 4 disulfide bridges, active on voltage-dependent K+ channel and also competing with apamin for binding to its receptor.
Kharrat
R
R
Laboratoire des Venins et Toxines, Institut Pasteur de Tunis, Tunis-Bélvédère, Tunisia.
Mansuelle
P
P
Sampieri
F
F
Crest
M
M
Oughideni
R
R
Van Rietschoten
J
J
Martin-Eauclaire
M F
MF
Rochat
H
H
El Ayeb
M
M
D000595:Amino Acid Sequence; D000818:Animals; D001030:Apamin / Q000378:metabolism; D003553:Cystine / Q000737:chemistry; D007928:Lethal Dose 50; D009682:Magnetic Resonance Spectroscopy; D051379:Mice; D008969:Molecular Sequence Data; D008970:Molecular Weight; D009498:Neurotoxins / Q000737:chemistry / Q000302:isolation & purification* / Q000378:metabolism / Q000494:pharmacology*; D015221:Potassium Channels / Q000187:drug effects* / Q000378:metabolism; D011487:Protein Conformation; D017433:Protein Structure, Secondary; D051381:Rats; D012604:Scorpion Venoms / Q000737:chemistry / Q000302:isolation & purification* / Q000378:metabolism / Q000494:pharmacology*; D016415:Sequence Alignment; D013574:Synaptosomes / Q000378:metabolism
D009498:Neurotoxins; D015221:Potassium Channels; D012604:Scorpion Venoms; C033799:apamin receptor; C072276:kaliotoxin; C104498:maurotoxin; D001030:Apamin; D003553:Cystine