title: Uncovering intense protein diversification in a cone snail venom gland using an integrative venomics approach.
abstract: Marine cone snail venoms are highly complex mixtures of peptides and proteins. They have been studied in-depth over the past 3 decades, but the modus operandi of the venomous apparatus still remains unclear. Using the fish-hunting Conus consors as a model, we present an integrative venomics approach, based on new proteomic results from the venom gland and data previously obtained from the transcriptome and the injectable venom. We describe here the complete peptide content of the dissected venom by the identification of numerous new peptides using nanospray tandem mass spectrometry in combination with transcriptomic data. Results reveal extensive mature peptide diversification mechanisms at work in the venom gland. In addition, by integrating data from three different venom stages, transcriptome, dissected, and injectable venoms, from a single species, we obtain a global overview of the venom processing that occurs from the venom gland tissue to the venom delivery step. In the light of the successive steps in this venom production system, we demonstrate that each venom compartment is highly specific in terms of peptide and protein content. Moreover, the integrated investigative approach discussed here could become an essential part of pharmaceutical development, as it provides new potential drug candidates and opens the door to numerous analogues generated by the very mechanisms used by nature to diversify its peptide and protein arsenal.
authors.affiliation: Atheris Laboratories , case postale 314, CH-1233 Bernex-Geneva, Switzerland.
authors.forename: Daniel
authors.initials: D
authors.lastname: Biass
authors.forename: Aude
authors.initials: A
authors.lastname: Violette
authors.forename: Nicolas
authors.initials: N
authors.lastname: Hulo
authors.forename: Frédérique
authors.initials: F
authors.lastname: Lisacek
authors.forename: Philippe
authors.initials: P
authors.lastname: Favreau
authors.forename: Reto
authors.initials: R
authors.lastname: Stöcklin
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002851:Chromatography, High Pressure Liquid; D020916:Conotoxins / Q000633:toxicity*; D052078:Conus Snail / Q000737:chemistry*; D013058:Mass Spectrometry; D008969:Molecular Sequence Data; D040901:Proteomics / Q000379:methods*; D017386:Sequence Homology, Amino Acid
chemical_list: D020916:Conotoxins
keywords: Cone snail; Conus consors; ESI-MS; conopeptide; mass spectrometry; nanotips emitter; peptide; peptidomics; transcriptomics; venomics