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

Aisha Manuwar,Ahmed Akrem,Christian Betzel,Hartmut Schlüter,Syed Abid Ali,Zia Mughal,Anwar Ullah,Benjamin Dreyer,Andreas Böhmert

doi:10.3390/toxins12110669

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.

Highlights

Pakistan has a particular geographical location and hosts an array of habitats such a, mountains, glaciers, coastal areas, swamps, plane areas, fresh water, and sandy areas [1]
Key Contribution: The present study describes a comprehensive overview of the venom proteome of Naja naja and Naja oxiana
The present study shows that N. naja and N. oxiana snake venom contain significant amounts of metalloproteinases, which are the second most abundant protein family

Summary

Introduction

Pakistan has a particular geographical location and hosts an array of habitats such a, mountains, glaciers, coastal areas, swamps, plane areas, fresh water, and sandy areas [1]. Nine habitat zones are recognized according to the distribution of snakes in Pakistan [2]. Seventy-two snake species are known to Pakistan, among which 14 marine and 12 terrestrial are venomous [1]. According to ITIS (Integrated Taxonomic Information System) database there are snake species belonging to the genus Naja [3]. Among these two are found in Pakistan, i.e., Naja naja and Naja oxiana [2]. Both of these snakes are non-spitting cobras [4].

Methods

Findings

Discussion

Conclusion