TxXIIIA, an atypical homodimeric conotoxin found in the Conus textile venom.
Venoms of predatory Conus snails are composed of several hundreds of peptide toxins. Many of these peptides display a high selectivity for particular membrane receptors such as ionic channels or G-protein coupled receptors. This property makes them very promising tools for the study of receptors and potential new drugs. Conus snails synthesize toxins under various folds, each fold related to particular pharmacological activities. Aiming the discovery of new conotoxins, we looked for toxins with original fold in the Conus textile venom by offline LC-MALDI-TOF/TOF mass spectrometry. Venom fractions were analysed by MALDI-TOF (in 2,5-dihydroxybenzoic acid) before and after the "in-solution" reduction of the disulfide bridges. Comparison of the spectra allows the classification of a large number of conotoxins according to the number of disulfide bridges. We focussed on a component at m/z 2785.7 (non-reduced)/ 1398.4 (reduced), which might represent a novel type of homodimeric toxin. The sequence TSDCCFYHNCCC was determined by De novo sequencing on the reduced species and represent a new fold. This sequence has already been described as the C-terminus part of a conotoxin scaffold IX precursor (expasy: Q9BPH1) but the power of our study resides in the fact that mass spectrometry highlights the right length of the toxin as well as its homodimeric form which could not be determined by the previous cDNA study. TxXIIIA is also the first homodimeric conotoxin with five disulfide bonds and composed of two monomers containing an odd number of cysteins.
Quinton
Loïc
L
Laboratoire de spectrométrie de masse, Centre d'Analyse des Résidus en Traces, GIGA-R, Université de Liège, Liège B-4000, Belgium. loic.quinton@ulg.ac.be
Gilles
Nicolas
N
De Pauw
Edwin
E
D000595:Amino Acid Sequence; D000818:Animals; D002853:Chromatography, Liquid / Q000379:methods; D020916:Conotoxins / Q000032:analysis* / Q000737:chemistry; D052078:Conus Snail; D003545:Cysteine / Q000737:chemistry; D019281:Dimerization; D004220:Disulfides / Q000737:chemistry; D008969:Molecular Sequence Data; D008978:Mollusk Venoms / Q000032:analysis* / Q000737:chemistry; D010455:Peptides / Q000737:chemistry; D017434:Protein Structure, Tertiary; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D013997:Time Factors
D020916:Conotoxins; D004220:Disulfides; D008978:Mollusk Venoms; D010455:Peptides; C541812:TxXIIIA toxin, Conus textile; D003545:Cysteine