Proteomic Investigations of Two Pakistani Naja Snake Venoms Species Unravel the Venom Complexity, Posttranslational Modifications, and Presence of Extracellular Vesicles

Abstract

Latest advancement of omics technologies allows in-depth characterization of venom compositions. In the present work we present a proteomic study of two snake venoms of the genus Naja i.e., Naja naja (black cobra) and Naja oxiana (brown cobra) of Pakistani origin. The present study has shown that these snake venoms consist of a highly diversified proteome. Furthermore, the data also revealed variation among closely related species. High throughput mass spectrometric analysis of the venom proteome allowed to identify for the N. naja venom 34 protein families and for the N. oxiana 24 protein families. The comparative evaluation of the two venoms showed that N. naja consists of a more complex venom proteome than N. oxiana venom. Analysis also showed N-terminal acetylation (N-ace) of a few proteins in both venoms. To the best of our knowledge, this is the first study revealing this posttranslational modification in snake venom. N-ace can shed light on the mechanism of regulation of venom proteins inside the venom gland. Furthermore, our data showed the presence of other body proteins, e.g., ankyrin repeats, leucine repeats, zinc finger, cobra serum albumin, transferrin, insulin, deoxyribonuclease-2-alpha, and other regulatory proteins in these venoms. Interestingly, our data identified Ras-GTpase type of proteins, which indicate the presence of extracellular vesicles in the venom. The data can support the production of distinct and specific anti-venoms and also allow a better understanding of the envenomation and mechanism of distribution of toxins. Data are available via ProteomeXchange with identifier PXD018726.

Multilevel Comparison of Indian Naja Venoms and Their Cross-Reactivity with Indian Polyvalent Antivenoms

“…Comparative analysis of venoms of N. naja and N. oxiana from Himachal Pradesh displayed substantial variation in venom proteomes. A similar observation was also made in a study investigating venom proteome profiles of Pakistani N. naja and N. oxiana [57].…”

Reply to Comments on Proteomic Investigations of Two Pakistani Naja Snake Venom Species Unravel the Venom Complexity, Posttranslational Modifications, and Presence of Extracellular Vesicles. Toxins 2020, 12, 669

“…In summary, the data, which we provided in our study and corresponding manuscript [6], are much more precise than many other, older published investigations not using the latest proteomics. However, the conclusion that can be drawn regarding the estimation of the overall toxic effects still is, of course, also approximated in our study.…”

Decomplexation of Venom Proteome of Pakistani Cobra (Naja naja naja)

“…This reflects the approach with which the venom analysis was performed and the region from where the snake specimen were collected. For example, the N. naja venom from South Punjab Pakistan showed the presence of three-finger toxins at 58 % [10] as compared to the northern side [5]. The decomplexation strategy however presents a much more detailed and comprehensive report of proteoforms [9].…”

“…Threefinger peptides (3FTx), Cysteine-rich secretory proteins (CRISPs), Nerve growth factor (NGF), Cobra venom factor (CVF), and natriuretic peptides are non-enzymatic proteinous molecules with toxic effects. These have been found in the venom of Naja specie in several studies [5,6]. Our study aimed to explore the venom proteome of the Pakistani cobra, N. naja from different geographical regions of Pakistan.…”