Proteotranscriptomic Analysis and Discovery of the Profile and Diversity of Toxin-like Proteins in Centipede

Abstract

SummaryCentipedes are one of the oldest venomous animals and use their venoms as weapons to attack prey or protect themselves. Their venoms contain various components with different biomedical and pharmacological properties. However, little attention has been paid to the profiles and diversity of their toxin-like proteins/peptides. In this study, we used a proteotranscriptomic approach to uncover the diversity of centipede toxin-like proteins in Scolopendra subspinipes mutilans. Nine hundred twentythree and 6,736 peptides, which were separately isolated from venom and torso tissues, respectively, were identified by ESI-MS/MS and deduced from their transcriptomes. Finally, 1,369 unique proteins were identified in the proteome, including 100 proteins that exhibited overlapping expression in venom and torso tissues. Of these proteins, at least 40 proteins were identified as venom toxin-like proteins. Meanwhile, transcriptome mining identified approximately 10-fold more toxin-like proteins and enabled the characterization of the precursor architecture of mature toxin-like peptides. Importantly, combined with proteomic and transcriptomic analyses, 25 toxin-like proteins/peptides (neurotoxins accounted for 50%) were expressed outside the venom gland and involved in gene recruitment processes. These findings highlight the extensive diversity of centipede toxin-like proteins and provide a new foundation for the medical-pharmaceutical use of centipede toxin-like proteins. Moreover, we are the first group to report the gene recruitment activity of venom toxin-like proteins in centipede, similar to snakes.

Recombinant Production and Characterization of a New Toxin from Cryptops iheringi Centipede Venom Revealed by Proteome and Transcriptome Analysis

“…The vast majority of studies of centipede venom are restricted to the Scolopendra genus [8][9][10]27,[29][30][31][32][33]. In addition, some studies use the whole centipede instead of the whole venom for their proteomics analyses, making a more specified comparison inviable [34,35]. Five comparative studies have demonstrated that centipede venoms are complex cocktails, encompassing more than 60 phylogenetically distinct protein families [10,32,[36][37][38].…”

Centipede Venom Peptides Acting on Ion Channels

“…Centipede venom contains an abundance of peptide toxins. With advances in transcriptomics and proteomics, the composition of centipede venom was confirmed through continuing effort [8,10,39,40]. Liu et al profiled the venom proteome and gland transcriptome from Scolopendra subspinipes dehaani and characterized 40 peptides [39].…”

“…Rong et al also focused on the diversity of centipede venom and obtained 79 unique peptide toxins from the venom of Scolopendra subspinipes mutilans [10]. Recently, Zhao et al identified 1204 unique proteins in the torso tissue and 165 unique proteins in the venom gland peptides of Scolopendra subspinipes mutilans using proteotranscriptomics [8].…”

“…The venom is also used to protect themselves from other predators or microorganisms. Centipede venom, containing large amounts of biogenic amines, serotonin, polysaccharides, lipids, peptide toxins and proteins [8], is a highly complex and functionally diverse mixture. For example, a glycosphingolipid from Parafontaria laminata armigera was reported to exert anticancer activity against melanoma cells by suppressing the focal adhesion kinase (FAK)-Akt pathway and the extracellular signal regulated kinase (Erk) 1/2 pathways [9].…”

“…Centipede bites produce extremely sharp pain in humans [1,5]. Human victims bitten by centipedes usually experience intense burning pain, redness, swelling, chills, fever and weakness [8,14]. Large centipedes occasionally produce superficial necrosis, myocardial ischemia and infarction, hematuria, hemoglobinuria, rhabdomyolysis, hemorrhage, pruritus, eosinophilic cellulitis, and anaphylaxis, sometimes in conjunction with organ failure and acute coronary ischemia [15][16][17][18][19].…”