Venom Proteomics of Indonesian King Cobra, Ophiophagus hannah: Integrating Top-Down and Bottom-Up Approaches
peer-reviewed · Journal of Proteome Research · 2015
| Date | 2015-06-05 |
| Type | peer-reviewed |
| Venue | Journal of Proteome Research |
| Publisher | American Chemical Society (ACS) |
| Contribution | downstream-application |
| DOI | 10.1021/acs.jproteome.5b00305 |
| Citations (OpenAlex) | 102 |
| Venue 2-year citedness | 3.83 |
Abstract
We report on the first application of top-down mass spectrometry in snake venomics. De novo sequence tags generated by, and ProSight Lite supported analysis of, combined collisional based dissotiations (CID and HCD) recorded in a hybrid LTQ Orbitrap instrument in data-dependent mode identified a number of proteins from different toxin families, namely, 11 three-finger toxins (7-7.9 kDa), a Kunitz-type inhibitor (6.3 kDa), ohanin (11.9 kDa), a novel phospholipase A2 molecule (13.8 kDa), and the cysteine-rich secretory protein (CRISP) ophanin (25 kDa) from Indonesian king cobra venom. Complementary bottom-up MS/MS analyses contributed to the completion of a locus-resolved venom phenotypic map for Ophiophagus hannah, the world’s longest venomous snake and a species of medical concern across its wide distribution range in forests from India to Southeast Asia. Its venom composition, comprising 32-35 proteins/peptides from 10 protein families, is dominated by α-neurotoxins and convincingly explains the main neurotoxic effects of human envenoming caused by king cobra bite. The integration of efficient chromatographic separation of the venom’s components and locus-resolved toxin identification through top-down and bottom-up MS/MS-based species-specific database searching and de novo sequencing holds promise that the future will be bright for the field of venom research.
Methods and tools
- Indonesian king cobra top-down venomics: Top-down and bottom-up venomics of Ophiophagus hannah, where de novo sequence tags from intact toxins identified three-finger toxins, a novel PLA2 and other proteins.
Data deposited
- Venom proteomics of Indonesian king cobra (as deposited) · PXD001726
Cites (4)
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- DeNovoGUI: An Open Source Graphical User Interface for de Novo Sequencing of Tandem Mass Spectra (2014) crossref
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Cited by (4)
- FT‐MS in the de novo top‐down sequencing of natural nontryptic peptides (2022) crossref
- Extended Snake Venomics by Top-Down In-Source Decay: Investigating the Newly Discovered Anatolian Meadow Viper Subspecies, Vipera anatolica senliki (2020) both
- Mass spectrometry-assisted venom profiling of Hypnale hypnale found in the Western Ghats of India incorporating de novo sequencing approaches (2018) crossref
- A Review and Database of Snake Venom Proteomes (2017) both