Academic Bibliography

 Search 200 years of publications by Ghent University researchers.
Advanced search
Add to list
  1. Search results
  2. Characterization of Amm VIII from And...

Characterization of Amm VIII from Androctonus mauretanicus mauretanicus : a new scorpion toxin that discriminates between neuronal and skeletal sodium channels

M Alami, H Vacher, Frank Bosmans (UGent) , C Devaux, JP Rosso, PE Bougis, J Tytgat, H Darbon and MF Martin-Eauclaire
(2003) BIOCHEMICAL JOURNAL. 375(3). p.551-560
Author
Organization
Abstract
The venom of the scorpion Androctonus mauretanicus mauretanicus was screened by use of a specific serum directed against AaH II, the scorpion a-toxin of reference, with the aim of identifying new analogues. This led to the isolation of Amm VIII (7382.57 Da), which gave a highly positive response in ELISA, but was totally devoid of toxicity when injected subcutaneously into mice. In voltage-clamp experiments with rat brain type II Na+ channel rNa(v) 1.2 or rat skeletal muscle Na+ channel rNa(v) 1.4, expressed in Xenopus oocytes, the EC50 values of the toxin-induced slowing of inactivation were: 29 +/- 5 and 416 +/- 14 nM respectively for AmmVIII and 2.6 +/- 0.3 nM and 2.2 +/- 0.2 nM, respectively, for AaH II interactions. Accordingly, Amm VIII clearly discriminates neuronal versus muscular Na+ channel. The Amm VIII cDNA was amplified from a venom gland cDNA library and its oligonucleotide sequence determined. It shows 87% sequence homology with AaH II, but carries an unusual extension at its C-terminal end, consisting of an additional Asp due to a point mutation in the cDNA penultimate codon. We hypothesized that this extra amino acid residue could induce steric hindrance and dramatically reduce recognition of the target by Amm VIII. We constructed a model of Amm VIII based on the Xray structure of AaH II to clarify this point. Molecular modelling showed that this C-terminal extension does not lead to an overall conformational change in Amm VIII, but drastically modifies the charge repartition and, consequently, the electrostatic dipole moment of the molecule. At last, liquid-phase radioimmunassays with poly- and monoclonal anti-(AaH II) antibodies showed the loss of conformational epitopes between AaH II and Amm VIII.
Keywords
cDNA, scorpion alpha-toxin, voltage-activated sodium channel, ALPHA-LIKE TOXINS, AUSTRALIS-HECTOR, FUNCTIONAL EXPRESSION, RECEPTOR-SITE, K+ CHANNELS, DIFFERENTIALLY INTERACT, MONOCLONAL-ANTIBODIES, MOLECULAR MECHANISMS, RAT-BRAIN, VENOM

Citation

Please use this url to cite or link to this publication:

MLA
Alami, M., et al. “Characterization of Amm VIII from Androctonus Mauretanicus Mauretanicus : A New Scorpion Toxin That Discriminates between Neuronal and Skeletal Sodium Channels.” BIOCHEMICAL JOURNAL, vol. 375, no. 3, 2003, pp. 551–60, doi:10.1042/bj20030688.
APA
Alami, M., Vacher, H., Bosmans, F., Devaux, C., Rosso, J., Bougis, P., … Martin-Eauclaire, M. (2003). Characterization of Amm VIII from Androctonus mauretanicus mauretanicus : a new scorpion toxin that discriminates between neuronal and skeletal sodium channels. BIOCHEMICAL JOURNAL, 375(3), 551–560. https://doi.org/10.1042/bj20030688
Chicago author-date
Alami, M, H Vacher, Frank Bosmans, C Devaux, JP Rosso, PE Bougis, J Tytgat, H Darbon, and MF Martin-Eauclaire. 2003. “Characterization of Amm VIII from Androctonus Mauretanicus Mauretanicus : A New Scorpion Toxin That Discriminates between Neuronal and Skeletal Sodium Channels.” BIOCHEMICAL JOURNAL 375 (3): 551–60. https://doi.org/10.1042/bj20030688.
Chicago author-date (all authors)
Alami, M, H Vacher, Frank Bosmans, C Devaux, JP Rosso, PE Bougis, J Tytgat, H Darbon, and MF Martin-Eauclaire. 2003. “Characterization of Amm VIII from Androctonus Mauretanicus Mauretanicus : A New Scorpion Toxin That Discriminates between Neuronal and Skeletal Sodium Channels.” BIOCHEMICAL JOURNAL 375 (3): 551–560. doi:10.1042/bj20030688.
Vancouver
1.
Alami M, Vacher H, Bosmans F, Devaux C, Rosso J, Bougis P, et al. Characterization of Amm VIII from Androctonus mauretanicus mauretanicus : a new scorpion toxin that discriminates between neuronal and skeletal sodium channels. BIOCHEMICAL JOURNAL. 2003;375(3):551–60.
IEEE
[1]
M. Alami et al., “Characterization of Amm VIII from Androctonus mauretanicus mauretanicus : a new scorpion toxin that discriminates between neuronal and skeletal sodium channels,” BIOCHEMICAL JOURNAL, vol. 375, no. 3, pp. 551–560, 2003.
@article{8584568,
  abstract     = {{The venom of the scorpion Androctonus mauretanicus mauretanicus was screened by use of a specific serum directed against AaH II, the scorpion a-toxin of reference, with the aim of identifying new analogues. This led to the isolation of Amm VIII (7382.57 Da), which gave a highly positive response in ELISA, but was totally devoid of toxicity when injected subcutaneously into mice. In voltage-clamp experiments with rat brain type II Na+ channel rNa(v) 1.2 or rat skeletal muscle Na+ channel rNa(v) 1.4, expressed in Xenopus oocytes, the EC50 values of the toxin-induced slowing of inactivation were: 29 +/- 5 and 416 +/- 14 nM respectively for AmmVIII and 2.6 +/- 0.3 nM and 2.2 +/- 0.2 nM, respectively, for AaH II interactions. Accordingly, Amm VIII clearly discriminates neuronal versus muscular Na+ channel. The Amm VIII cDNA was amplified from a venom gland cDNA library and its oligonucleotide sequence determined. It shows 87% sequence homology with AaH II, but carries an unusual extension at its C-terminal end, consisting of an additional Asp due to a point mutation in the cDNA penultimate codon. We hypothesized that this extra amino acid residue could induce steric hindrance and dramatically reduce recognition of the target by Amm VIII. We constructed a model of Amm VIII based on the Xray structure of AaH II to clarify this point. Molecular modelling showed that this C-terminal extension does not lead to an overall conformational change in Amm VIII, but drastically modifies the charge repartition and, consequently, the electrostatic dipole moment of the molecule. At last, liquid-phase radioimmunassays with poly- and monoclonal anti-(AaH II) antibodies showed the loss of conformational epitopes between AaH II and Amm VIII.}},
  author       = {{Alami, M and Vacher, H and Bosmans, Frank and Devaux, C and Rosso, JP and Bougis, PE and Tytgat, J and Darbon, H and Martin-Eauclaire, MF}},
  issn         = {{0264-6021}},
  journal      = {{BIOCHEMICAL JOURNAL}},
  keywords     = {{cDNA,scorpion alpha-toxin,voltage-activated sodium channel,ALPHA-LIKE TOXINS,AUSTRALIS-HECTOR,FUNCTIONAL EXPRESSION,RECEPTOR-SITE,K+ CHANNELS,DIFFERENTIALLY INTERACT,MONOCLONAL-ANTIBODIES,MOLECULAR MECHANISMS,RAT-BRAIN,VENOM}},
  language     = {{eng}},
  number       = {{3}},
  pages        = {{551--560}},
  title        = {{Characterization of Amm VIII from Androctonus mauretanicus mauretanicus : a new scorpion toxin that discriminates between neuronal and skeletal sodium channels}},
  url          = {{http://doi.org/10.1042/bj20030688}},
  volume       = {{375}},
  year         = {{2003}},
}
Altmetric
View in Altmetric
Web of Science
Times cited: