Uncovering Intense Protein Diversification in a Cone Snail Venom Gland Using an Integrative Venomics Approach

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.