Venomous snakes possess a sophisticated system for biological warfare, consisting primarily of a complex cocktail of pharmacologically active proteins and peptides that facilitate immobilisation, killing, and digestion of prey, which has inspired research endeavours in both antivenom development and venom-derived drug design. Such snake venoms possess a distinct complexity compared to those of other animals, comprised of an exceptionally diverse array of proteins and post-translational modifications. In addition, a significant gap in knowledge exists in terms of higher-order interactions between proteins proposed to modulate venom potency. Consequently, snake venoms not only present a challenge for current proteomics approaches to fully categorise and quantify the range of proteoforms present, but also an opportunity to apply new integrated mass spectrometry-based platforms for characterisation.
This presentation will describe ongoing research aimed at enhancing top-down mass spectrometry (MS) based methodologies for venomics, reliant on capabilities in ion mobility (IM)-MS, protein derivatisation and native MS. By implementing a complex-centric proteomic profiling platform that enables improved detection and quantification of intact proteins and proteoforms, we describe venom protein interactomes for selected snakes of medical significance with greater detail and throughput. This work also emphasises the importance of understanding higher-order protein interactions in venom activity.