title: Diversity in sequences, post-translational modifications and expected pharmacological activities of toxins from four Conus species revealed by the combination of cutting-edge proteomics, transcriptomics and bioinformatics.
abstract: Venomous animals have developed a huge arsenal of reticulated peptides for defense and predation. Based on various scaffolds, they represent a colossal pharmacological diversity, making them top candidates for the development of innovative drugs. Instead of relying on the classical, low-throughput bioassay-guided approach to identify innovative bioactive peptides, this work exploits a recent paradigm to access to venom diversity. This strategy bypasses the classical approach by combining high-throughput transcriptomics, proteomics and bioinformatics cutting-edge technologies to generate reliable peptide sequences. The strategy employed to generate hundreds of reliable sequences from Conus venoms is deeply described. The study led to the discovery of (i) conotoxins that belong to known pharmacological families targeting various GPCRs or ion-gated channels, and (ii) new families of conotoxins, never described to date. It also focusses on the diversity of genes, sequences, folds, and PTM's provided by such species.
authors.affiliation: Laboratory of Mass Spectrometry, MolSys, ULg, Liege, Belgium.
authors.forename: Michel
authors.initials: M
authors.lastname: Degueldre
authors.affiliation: iBiTEc S/SPI Antibody Eng. for Health, CEA, Gif-sur-Yvette, France.
authors.forename: Marion
authors.initials: M
authors.lastname: Verdenaud
authors.affiliation: Bioinformatics Department, Sistemas Genomicos Ltd, Valencia, Spain.
authors.forename: Garikoitz
authors.initials: G
authors.lastname: Legarda
authors.affiliation: Bioinformatics Department, Sistemas Genomicos Ltd, Valencia, Spain.
authors.forename: Rebeca
authors.initials: R
authors.lastname: Minambres
authors.affiliation: Bioinformatics Department, Sistemas Genomicos Ltd, Valencia, Spain.
authors.forename: Sheila
authors.initials: S
authors.lastname: Zuniga
authors.affiliation: Venometech, Valbonne, France.
authors.forename: Mathieu
authors.initials: M
authors.lastname: Leblanc
authors.affiliation: iBiTec-S, SIMOPRO, CEA, Gif-Sur-Yvette, France.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Gilles
authors.affiliation: iBiTEc S/SPI Antibody Eng. for Health, CEA, Gif-sur-Yvette, France.
authors.forename: Frederic
authors.initials: F
authors.lastname: Ducancel
authors.affiliation: Laboratory of Mass Spectrometry, MolSys, ULg, Liege, Belgium.
authors.forename: Edwin
authors.initials: E
authors.lastname: De Pauw
authors.affiliation: Laboratory of Mass Spectrometry, MolSys, ULg, Liege, Belgium. Electronic address: loic.quinton@ulg.ac.be.
authors.forename: Loic
authors.initials: L
authors.lastname: Quinton
mesh_terms: D000818:Animals; D002853:Chromatography, Liquid; D019295:Computational Biology / Q000379:methods; D052078:Conus Snail / Q000378:metabolism; D020869:Gene Expression Profiling; D008978:Mollusk Venoms / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology; D010802:Phylogeny; D020033:Protein Isoforms; D011499:Protein Processing, Post-Translational; D040901:Proteomics / Q000379:methods; D017423:Sequence Analysis, RNA; D053719:Tandem Mass Spectrometry
chemical_list: D008978:Mollusk Venoms; D020033:Protein Isoforms
keywords: Bioinformatics; Cone snail; Diversity; Proteomics; Transcriptomics; Venomics