Investigating Toxin Diversity and Abundance in Snake Venom Proteomes

Abstract

Understanding snake venom proteomes is becoming increasingly important to understand snake venom biology, evolution and especially clinical effects of venoms and approaches to antivenom development. To explore the current state of snake venom proteomics and transcriptomics we investigated venom proteomic methods, associations between methodological and biological variability and the diversity and abundance of protein families. We reviewed available studies on snake venom proteomes from September 2017 to April 2021. This included 81 studies characterising venom proteomes of 79 snake species, providing data on relative toxin abundance for 70 species and toxin diversity (number of different toxins) for 37 species. Methodologies utilised in these studies were summarised and compared. Several comparative studies showed that preliminary decomplexation of crude venom by chromatography leads to increased protein identification, as does the use of transcriptomics. Combining different methodological strategies in venomic approaches appears to maximize proteome coverage. 48% of studies used the RP-HPLC →1D SDS-PAGE →in-gel trypsin digestion → ESI -LC-MS/MS pathway. Protein quantification by MS1-based spectral intensity was used twice as commonly as MS2-based spectral counting (33–15 studies). Total toxin diversity was 25–225 toxins/species, with a median of 48. The relative mean abundance of the four dominant protein families was for elapids; 3FTx–52%, PLA2–27%, SVMP–2.8%, and SVSP–0.1%, and for vipers: 3FTx–0.5%, PLA2–24%, SVMP–27%, and SVSP–12%. Viper venoms were compositionally more complex than elapid venoms in terms of number of protein families making up most of the venom, in contrast, elapid venoms were made up of fewer, but more toxin diverse, protein families. No relationship was observed between relative toxin diversity and abundance. For equivalent comparisons to be made between studies, there is a need to clarify the differences between methodological approaches and for acceptance of a standardised protein classification, nomenclature and reporting procedure. Correctly measuring and comparing toxin diversity and abundance is essential for understanding biological, clinical and evolutionary implications of snake venom composition.

The Unusual Metalloprotease-Rich Venom Proteome of the Australian Elapid Snake Hoplocephalus stephensii

“…Globally, elapid venoms have been shown to mostly be composed of low-molecular-weight toxins belonging to the protein families 3FTx and/or PLA 2 . Combined, these two dominant toxin families typically make up almost 80% of elapid venoms [ 19 , 20 ]. In contrast, we show that almost half of the venom of H. stephensii is made up of high-molecular-weight proteins—SVMP (36.7%) and LAAO (10.8%).…”

“…Although approximately 50 different protein families have been identified in snake venoms worldwide, most snake venoms have been shown to be largely composed of four dominant protein families; three-finger toxins (3FTx), phospholipase A 2 (PLA 2 ), snake venom metalloprotease (SVMP), snake venom serine protease (SVSP), and six secondary protein families; L-amino acid oxidase (LAAO), kunitz peptides (KUN), cysteine-rich secretory proteins (CRiSP), natriuretic peptides (NP), C-type lectins (CTL), and disintegrins (DIS) [ 19 , 20 ].…”

“…Despite the long history of research in characterizing the pharmacology of toxins in the venoms of the Hydrophiinae subfamily, the venom composition of the species in this subfamily remains the least characterized of any group of elapids or vipers [ 19 , 20 ]. We aimed to determine the venom composition of Stephen’s banded snake H. stephensii to investigate venom expression in a morphologically and ecologically specialized elapid.…”

Antiviral Effects of Animal Toxins: Is There a Way to Drugs?

“…Despite such a big diversity, the number of protein or peptide structural families represented in animal venoms is not very large. For example, about two dozen families can be found in snake venoms [ 9 ]. The most abundant families of snake toxins are phospholipases A2 (PLA2), three-finger toxins (3FTx), snake venom serine proteases (SVSP), and snake venom metalloprotease (SVMP).…”

Editorial: Venoms and Toxins: Functional Omics and Pharmacological Insights

“…In addition, the proteomic analysis unveiled the richness of pharmacologically active molecules in the species’ venom, suggesting its potential for drug discovery. The second in-depth review article, by Tasoulis et al (2022) , explored the current state of venom proteomic methods, associations between methodological and biological variability and the diversity and abundance of protein families, reported for snake venom proteomes from September 2017 to April 2021. The review included a total of 81 venom proteomic studies of 79 snake species, where relative toxin abundance was reported for 70 species and toxin diversity (number of different toxins) was reported for 37 species.…”