Snake Venom Extracellular vesicles (SVEVs) reveal wide molecular and functional proteome diversity

Abstract

Proteins constitute almost 95% of snake venom’s dry weight and are produced and released by venom glands in a solubilized form during a snake bite. These proteins are responsible for inducing several pharmacological effects aiming to immobilize and initiate the pre-digestion of the prey. This study shows that proteins can be secreted and confined in snake venom extracellular vesicles (SVEVs) presenting a size distribution between 50 nm and 500 nm. SVEVs isolated from lyophilized venoms collected from four different species of snakes (Agkistrodon contortrix contortrix, Crotalus atrox, Crotalus viridis and Crotalus cerberus oreganus) were analyzed by mass spectrometry-based proteomic, which allowed the identification of proteins belonging to eight main functional protein classes such as SVMPs, serine proteinases, PLA2, LAAO, 5′nucleotidase, C-type lectin, CRISP and Disintegrin. Biochemical assays indicated that SVEVs are functionally active, showing high metalloproteinase and fibrinogenolytic activity besides being cytotoxic against HUVEC cells. Overall, this study comprehensively depicts the protein composition of SVEVs for the first time. In addition, the molecular function of some of the described proteins suggests a central role for SVEVs in the cytotoxicity of the snake venom and sheds new light in the envenomation process.

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

“…The size distribution of SVEVs was found to be between approximately 50–500 nm. Proteomic investigations revealed that SVEVs could be assigned to eight different protein classes, such as SVMP, SVSP, and disintegrins [ 135 ].…”

Vipers of the Middle East: A Rich Source of Bioactive Molecules

“…Other components include carbohydrates, lipids, metal ions, and inorganic anions. The most common enzymes include phospholipase A2 (PLA2), hyaluronidase, metalloproteases, l -amino acid oxidase ( l -AAO), acetylcholinesterases, and serine proteases [ 10 ].…”

Origin and Characterization of Extracellular Vesicles Present in the Spider Venom of Ornithoctonus hainana

“…However, the EVs reported in the venom of venomous animals are known by different names, including microvesicles ( Crotalus durissus terrificus ) [ 16 ], exosome-like vesicles ( Gloydius blomhoffi blomhoffi ) [ 17 ], small membranous vesicles ( Gloydius blomhoffi blomhoffi ) [ 18 ], mixed-strategy extracellular vesicles ( Leptopilina heterotoma ) [ 19 ], venosomes ( Leptopilina heterotoma and Leptopilina boulardi ) [ 20 ], and extracellular vesicles ( Leptopilina heterotoma ) [ 21 ]. The functional molecules in the EVs of snake ( Agkistrodon contortrix ) venom are primarily virulence-related proteins, with significant cytotoxic activity [ 22 ]. Parasitoid wasp venom EVs contain immunosuppressive proteins that can target and kill the Drosophila’s lamellocyte, increasing the success of wasp parasitism on certain Drosophila species [ 19 , 20 ].…”