Disulfide bridge reorganization induced by proline mutations in maurotoxin

FEBS Letters

Brocard, J.¹  Darbon, H.³  Rochat, H.²  de Waard, M.¹  Mansuelle, P.²  Geib, S.¹  Oughideni, R.²  Sandoz, G.¹  Regaya, I.²  Sabatier, J.M.²  Devaux, C.²  Carlier, E.¹  Fathallah, M.²  Di Luccio, E.²  Mosbah, A.³  Fajloun, Z.² 

[1] Laboratoire de Neurobiologie des Canaux Ioniques, INSERM U464, IFR Jean Roche, Faculté de Médecine Nord, Bd Pierre Dramard, 13916 Marseille Cedex 20, France;Laboratoire de Biochimie, CNRS UMR 6560, IFR Jean Roche, Faculté de Médecine Nord, Bd Pierre Dramard, 13916 Marseille Cedex 20, France;AFMB, CNRS UPR 9039, IFR1, 31 Chemin Joseph-Aiguier, 13402 Marseille Cedex 20, France

关键词: Maurotoxin;    Scorpion toxin;    Potassium channel;    Synthetic peptide;    Half-cystine pairing;    Xenopus oocyte;    HPLC;    high-pressure liquid chromatography;    MTX;    maurotoxin;    a scorpion toxin from the venom of Scorpio maurus palmatus;    Pi1;    a scorpion toxin from the venom of Pandinus imperator;    HsTx1;    toxin 1 from the venom of the scorpion Heterometrus spinnifer;   

DOI  :  10.1016/S0014-5793(00)02433-9

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

Maurotoxin (MTX) is a 34-residue toxin that has been isolated from the venom of the chactidae scorpion Scorpio maurus palmatus, and characterized. Together with Pi1 and HsTx1, MTX belongs to a family of short-chain four-disulfide-bridged scorpion toxins acting on potassium channels. However, contrary to other members of this family, MTX exhibits an uncommon disulfide bridge organization of the type C1–C5, C2–C6, C3–C4 and C7–C8, versus C1–C5, C2–C6, C3–C7 and C4–C8 for both Pi1 and HsTx1. Here, we report that the substitution of MTX proline residues located at positions 12 and/or 20, adjacent to C3 (Cys₁₃) and C4 (Cys₁₉), results in conventional Pi1- and HsTx1-like arrangement of the half-cystine pairings. In this case, this novel disulfide bridge arrangement is without obvious incidence on the overall three-dimensional structure of the toxin. Pharmacological assays of this structural analog, [A₁₂,A₂₀]MTX, reveal that the blocking activities on Shaker B and rat Kv1.2 channels remain potent whereas the peptide becomes inactive on rat Kv1.3. These data indicate, for the first time, that discrete point mutations in MTX can result in a marked reorganization of the half-cystine pairings, accompanied with a novel pharmacological profile for the analog.

【 授权许可】

Unknown