Exploring snake venom proteomes: multifaceted analyses for complex toxin mixtures

Abstract

Snake venom proteomes are complex mixtures of a large number of distinct proteins. In a sense, the field of snake venom proteomics has been under investigation since the very earliest biochemical studies on venoms where peptides and proteins were isolated and structurally and biologically characterized. With the recent developments in mass spectrometry for the identification of proteins, coupled with venom gland transcriptomes, has the field of snake venom proteomics began to flourish. These developments have led to exciting insights into the protein composition of venoms and subsequently their pathological activities. In this review, we will discuss the state of art of snake venom proteomics. Although we have not reached the ultimate goal of characterizing and quantifying all unique proteins in a venom proteome, current technologies have opened many opportunities for high-throughput proteomic studies that have gone beyond simple protein identification to analyzing various functional aspects, such as post-translational modifications, proteolytic processing and toxin-target interactions. In this review, we will discuss the technological approaches used in the study of venom proteomics highlighting the advances made and future directions.

Mapping Proteoforms and Protein Complexes From King Cobra Venom Using Both Denaturing and Native Top-down Proteomics

“…Comparing our BU identifications to recently published papers that used BU for protein identification in O. hannah venom, we were able to identify 80 and 40% more protein families than the identifications presented by Petras et al (21) and Vonk and co-workers (36), respectively. Notable differences may be related to the different methodologies applied, instrumentation used, and/or variation in snake venom sample (4,7,8). Our BU quantitation results showed large amounts of 3FTx in the venom that is consistent with the previous studies of the king cobra venom proteome (21,36,67) and with the rapid neurotoxicity because of muscular transmission blockage (i.e.…”

“…Snakes produce anywhere from three to several dozen diverse families of toxic proteins. Each family is encoded by multiple multilocus genes generated by gene duplication resulting in a large number of expressed isoforms (6) that can differ greatly even between individuals of the same species (4,7,8).…”

Exploring the venom proteome of the African puff adder, Bitis arietans, using a combinatorial peptide ligand library approach at different pHs

“…Recent contributions of the literature of snake venom have underscored the need for multifaceted approaches for maximizing proteome coverage [19][20][21]. Very recently we have applied two solid-phase combinatorial hexapeptide ligand libraries to explore the occurrence of low-abundance proteins in the venom of Crotalus atrox [22].…”

The Toxicogenomic Multiverse: Convergent Recruitment of Proteins Into Animal Venoms

“…Venoms across the Kingdom Animalia are complex mixtures that include variable combinations of proteins (ranging from multiunit globular enzymes to small peptides), salts, and organic molecules such as polyamines, amino acids, and neurotransmitters (49,54,72,117,144). Proteins found in venoms are the result of toxin recruitment events in which an ordinary protein gene, typically one involved in a key regulatory process, is duplicated, and the new gene is selectively expressed in the venom gland.…”