Venomic and Transcriptomic Analysis of Centipede Scolopendra subspinipes dehaani

Abstract

Centipedes have venom glands in their first pair of limbs, and their venoms contain a large number of components with different biochemical and pharmacological properties. However, information about the compositions and functions of their venoms is largely unknown. In this study, Scolopendra subspinipes dehaani venoms were systematically investigated by transcriptomic and proteomic analysis coupled with biological function assays. After random screening approximately 1500 independent clones, 1122 full length cDNA sequences, which encode 543 different proteins, were cloned from a constructed cDNA library using a pair of venom glands from a single centipede species. Neurotoxins, ion channel acting components and venom allergens were the main fractions of the crude venom as revealed by transcriptomic analysis. Meanwhile, 40 proteins/peptides were purified and characterized from crude venom of S. subspinipes dehaani. The N-terminal amino acid sequencing and mass spectrum results of 29 out of these 40 proteins or peptides matched well with their corresponding cDNAs. The purified proteins/peptides showed different pharmacological properties, including the following: (1) platelet aggregating activity; (2) anticoagulant activity; (3) phospholipase A(2) activity; (4) trypsin inhibiting activity; (5) voltage-gated potassium channel activities; (6) voltage-gated sodium channel activities; (7) voltage-gated calcium channel activities. Most of them showed no significant similarity to other protein sequences deposited in the known public database. This work provides the largest number of protein or peptide candidates with medical-pharmaceutical significance and reveals the toxin nature of centipede S. subspinipes dehaani venom.

Centipede venoms as a source of drug leads

“…The venom peptides, which are of most interest from a drug discovery perspective, are extraordinarily diverse [25,[27][28][29][30][31][32]. Undheim et al [30] classified centipede venom peptides into 31 phylogenetically distinct families of scutigerotoxins (SCUTX1-3) and scoloptoxins ( .…”

“…However, centipede HAND toxins have undergone greater radiation than those in spiders, with the HAND-form accounting for the vast majority of molecular diversity in the SLPTX3 family [29][30][31]. In centipede HAND toxins, one turn of α3 was excised to remove the residues between cysteines 4 and 5, thereby creating a highly compact and ultrastable peptide fold [21,35].…”

“…for example, numerous centipede-venom peptides have been isolated that inhibit Na V , Ca V , and K V channels in rat dorsal root ganglion sensory neurons [28,29,57]. Small, non-reticulated peptides with antimicrobial activity have also been isolated from centipede venoms [58,59].…”

“…SSD609 is a 47-residue peptide first purified from venom of Scolopendra subspinipes dehaani [29]. It is a member of the SPLTX3 family of toxins and is closely related to Ssm6a; its name based on the rational nomenclature proposed for centipede-venom peptides is κ-SLPTX 3 -Sd1a.…”

“…Remarkably, despite this taxonomic bias, the small number of studies undertaken to date have revealed that centipede venoms contain a remarkable diversity of disulfide-rich peptides that encompass a greater variety of constrained peptide scaffolds than present in any other venom [27][28][29][30].…”