In-Depth Venome of the Brazilian Rattlesnake Crotalus durissus terrificus: An Integrative Approach Combining Its Venom Gland Transcriptome and Venom Proteome

Abstract

Snake venoms are complex mixtures mainly composed of proteins and small peptides. Crotoxin is one of the most studied components from Crotalus venoms, but many other components are less known due to their low abundance. The venome of Crotalus durissus terrificus, the most lethal Brazilian snake, was investigated by combining its venom gland transcriptome and proteome to create a holistic database of venom compounds unraveling novel toxins. We constructed a cDNA library from C. d. terrificus venom gland using the Illumina platform and investigated its venom proteome through high resolution liquid chromotography–tandem mass spectrometry. After integrating data from both data sets, more than 30 venom components classes were identified by the transcriptomic analysis and 15 of them were detected in the venom proteome. However, few of them (PLA2, SVMP, SVSP, and VEGF) were relatively abundant. Furthermore, only seven expressed transcripts contributed to ∼82% and ∼73% of the abundance in the transcriptome and proteome, respectively. Additionally, novel venom proteins are reported, and we highlight the importance of using different databases to perform the data integration and discuss the structure of the venom components-related transcripts identified. Concluding, this research paves the way for novel investigations and discovery of future pharmacological agents or targets in the antivenom therapy.

Geographic variation of individual venom profile of Crotalus durissus snakes

“…The high intraspecific variability regarding LAAO activity was expected based on the compositional characterization of C. durissus ssp. described herein and in previous reports [ 20 , 21 ].…”

“…The pro-coagulant activity exerted by C. durissus ssp. venom is mainly due to the action of the serine proteinase gyroxin [ 36 , 37 ], although C-type lectins and metalloproteinases, even in low amounts as those reported in the venom of this species [ 4 , 21 , 37 ], may also be involved.…”

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

“…Recent scientific advances have paved the way to explore venomous snake composition in detail and various strategies have been evolved to better understand venom components, their function and immunological properties [ 27 ]. Genomic and transcriptomic studies have proved to be an invaluable tool in the discovery of the snake venom evolution and proteoform [ 28 , 29 , 30 , 31 , 32 , 33 , 34 ]. Consequently, investigations are directed towards the discovery of pharmacologically active snake venom compounds [ 35 , 36 , 37 , 38 ].…”

Cell-Penetrating Peptides Derived from Animal Venoms and Toxins

“…As a result of millions of years of evolution, the diversity of molecular structures and activities is immeasurable, with hidden functions and structures only recently disclosed by modern omics techniques associated with classical pharmacological studies [3]. Thus, the holistic molecular genetic analyses of venomous animals utilizing, for example, transcriptome in combination with proteome studies of venom glands, have revealed not only the diversity of a set of substances produced by a given organism that inhabits a particular biome but also the uniqueness of such molecular repertoire expressed as active components of biological materials, such as venoms [4][5][6][7][8].…”