Maurotoxin versus Pi1/HsTx1 scorpion toxins. Toward new insights in the understanding of their distinct disulfide bridge patterns.
Maurotoxin (MTX) is a scorpion toxin acting on several K(+) channel subtypes. It is a 34-residue peptide cross-linked by four disulfide bridges that are in an "uncommon" arrangement of the type C1-C5, C2-C6, C3-C4, and C7-C8 (versus C1-C5, C2-C6, C3-C7, and C4-C8 for Pi1 or HsTx1, two MTX-related scorpion toxins). We report here that a single mutation in MTX, in either position 15 or 33, resulted in a shift from the MTX toward the Pi1/HsTx1 disulfide bridge pattern. This shift is accompanied by structural and pharmacological changes of the peptide without altering the general alpha/beta scaffold of scorpion toxins.
Fajloun
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CNRS UMR 6560, Boulevard Pierre Dramard, 13916 Marseille Cedex 20, the Architecture et Fonction des Macromolécules Biologiques, CNRS UPR 9039, 31 Chemin Joseph Aiguier, 13402 Marseille, France.
Mosbah
A
A
Carlier
E
E
Mansuelle
P
P
Sandoz
G
G
Fathallah
M
M
di Luccio
E
E
Devaux
C
C
Rochat
H
H
Darbon
H
H
De Waard
M
M
Sabatier
J M
JM
D000595:Amino Acid Sequence; D000818:Animals; D001921:Brain / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid; D003545:Cysteine / Q000737:chemistry; D004220:Disulfides; D004305:Dose-Response Relationship, Drug; D004594:Electrophysiology; D007700:Kinetics; D007928:Lethal Dose 50; D008024:Ligands; D009682:Magnetic Resonance Spectroscopy; D051379:Mice; D008810:Mice, Inbred C57BL; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009154:Mutation; D009865:Oocytes / Q000378:metabolism; D010452:Peptide Biosynthesis; D017354:Point Mutation; D015221:Potassium Channels / Q000737:chemistry; D011487:Protein Conformation; D017433:Protein Structure, Secondary; D051381:Rats; D012604:Scorpion Venoms / Q000737:chemistry* / Q000235:genetics; D017386:Sequence Homology, Amino Acid; D013574:Synaptosomes / Q000378:metabolism; D013997:Time Factors; D014981:Xenopus
D004220:Disulfides; D008024:Ligands; C104751:Pi1 toxin; D015221:Potassium Channels; D012604:Scorpion Venoms; C109471:TX1 toxin, Heterometrus spinnifer; C104498:maurotoxin; D003545:Cysteine