A new type of scorpion Na+-channel-toxin-like polypeptide active on K+ channels

Najet Srairi-Abid, Joseba Iñaki Guijarro, Rym Benkhalifa, Massimo Mantegazza, Amani Cheikh, Manel Ben Aissa, Pierre Yves Haumont, Muriel Delepierre, Mohamed El Ayeb

Research output: Contribution to journalArticle

30 Citations (Scopus)

Abstract

We have purified and characterized two peptides, named KAaH1 and KAaH2 (AaH polypeptides 1 and 2 active on K+ channels, where AaH stands for Androctonus australis Hector), from the venom of A. australis Hector scorpions. Their sequences contain 58 amino acids including six half-cysteines and differ only at positions 26 (Phe/Ser) and 29 (Lys/Gln). Although KAaH1 and KAaH2 show important sequence similarity with anti-mammal β toxins specific for voltage-gated Na+ channels, only weak β-like effects were observed when KAaH1 or KAaH2 (1 μM) were tested on brain Nav1.2 channels. In contrast, KAaH1 blocks Kv1.1 and Kv1.3 channels expressed in Xenopus oocytes with IC50 values of 5 and 50 nM respectively, whereas KAaH2 blocks only 20% of the current on Kv1.1 and is not active on Kv1.3 channels at a 100 nM concentration. KAaH1 is thus the first member of a new subfamily of long-chain toxins mainly active on voltage-gated K+ channels. NMR spectra of KAaH1 and KAaH2 show good dispersion of signals but broad lines and poor quality. Self-diffusion NMR experiments indicate that lines are broadened due to a conformational exchange on the millisecond time scale. NMR and CD indicate that both polypeptides adopt a similar fold with α-helical and β-sheet structures. Homology-based molecular models generated for KAaH1 and KAaH2 are in accordance with CD and NMR data. In the model of KAaH1, the functionally important residues Phe26 and Lys29 are close to each other and are located in the α-helix. These residues may constitute the so-called functional dyad observed for short α-KTx scorpion toxins in the β-sheet.

Original languageEnglish
Pages (from-to)455-464
Number of pages10
JournalBiochemical Journal
Volume388
Issue number2
DOIs
Publication statusPublished - Jun 1 2005

Fingerprint

Scorpions
Nuclear magnetic resonance
Peptides
Voltage-Gated Potassium Channels
Molecular Models
Venoms
Xenopus
Inhibitory Concentration 50
Mammals
Oocytes
Cysteine
Amino Acids
Brain
Electric potential
Experiments

Keywords

  • Androctonus australis scorpion
  • dyad F/K
  • K channel
  • Na channel
  • Scorpion toxin
  • Structure-function relationship

ASJC Scopus subject areas

  • Biochemistry

Cite this

Srairi-Abid, N., Guijarro, J. I., Benkhalifa, R., Mantegazza, M., Cheikh, A., Ben Aissa, M., ... El Ayeb, M. (2005). A new type of scorpion Na+-channel-toxin-like polypeptide active on K+ channels. Biochemical Journal, 388(2), 455-464. https://doi.org/10.1042/BJ20041407

A new type of scorpion Na+-channel-toxin-like polypeptide active on K+ channels. / Srairi-Abid, Najet; Guijarro, Joseba Iñaki; Benkhalifa, Rym; Mantegazza, Massimo; Cheikh, Amani; Ben Aissa, Manel; Haumont, Pierre Yves; Delepierre, Muriel; El Ayeb, Mohamed.

In: Biochemical Journal, Vol. 388, No. 2, 01.06.2005, p. 455-464.

Research output: Contribution to journalArticle

Srairi-Abid, N, Guijarro, JI, Benkhalifa, R, Mantegazza, M, Cheikh, A, Ben Aissa, M, Haumont, PY, Delepierre, M & El Ayeb, M 2005, 'A new type of scorpion Na+-channel-toxin-like polypeptide active on K+ channels', Biochemical Journal, vol. 388, no. 2, pp. 455-464. https://doi.org/10.1042/BJ20041407
Srairi-Abid N, Guijarro JI, Benkhalifa R, Mantegazza M, Cheikh A, Ben Aissa M et al. A new type of scorpion Na+-channel-toxin-like polypeptide active on K+ channels. Biochemical Journal. 2005 Jun 1;388(2):455-464. https://doi.org/10.1042/BJ20041407
Srairi-Abid, Najet ; Guijarro, Joseba Iñaki ; Benkhalifa, Rym ; Mantegazza, Massimo ; Cheikh, Amani ; Ben Aissa, Manel ; Haumont, Pierre Yves ; Delepierre, Muriel ; El Ayeb, Mohamed. / A new type of scorpion Na+-channel-toxin-like polypeptide active on K+ channels. In: Biochemical Journal. 2005 ; Vol. 388, No. 2. pp. 455-464.
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AU - Mantegazza, Massimo

AU - Cheikh, Amani

AU - Ben Aissa, Manel

AU - Haumont, Pierre Yves

AU - Delepierre, Muriel

AU - El Ayeb, Mohamed

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N2 - We have purified and characterized two peptides, named KAaH1 and KAaH2 (AaH polypeptides 1 and 2 active on K+ channels, where AaH stands for Androctonus australis Hector), from the venom of A. australis Hector scorpions. Their sequences contain 58 amino acids including six half-cysteines and differ only at positions 26 (Phe/Ser) and 29 (Lys/Gln). Although KAaH1 and KAaH2 show important sequence similarity with anti-mammal β toxins specific for voltage-gated Na+ channels, only weak β-like effects were observed when KAaH1 or KAaH2 (1 μM) were tested on brain Nav1.2 channels. In contrast, KAaH1 blocks Kv1.1 and Kv1.3 channels expressed in Xenopus oocytes with IC50 values of 5 and 50 nM respectively, whereas KAaH2 blocks only 20% of the current on Kv1.1 and is not active on Kv1.3 channels at a 100 nM concentration. KAaH1 is thus the first member of a new subfamily of long-chain toxins mainly active on voltage-gated K+ channels. NMR spectra of KAaH1 and KAaH2 show good dispersion of signals but broad lines and poor quality. Self-diffusion NMR experiments indicate that lines are broadened due to a conformational exchange on the millisecond time scale. NMR and CD indicate that both polypeptides adopt a similar fold with α-helical and β-sheet structures. Homology-based molecular models generated for KAaH1 and KAaH2 are in accordance with CD and NMR data. In the model of KAaH1, the functionally important residues Phe26 and Lys29 are close to each other and are located in the α-helix. These residues may constitute the so-called functional dyad observed for short α-KTx scorpion toxins in the β-sheet.

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KW - K channel

KW - Na channel

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KW - Structure-function relationship

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