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Venom gland transcriptome and venom proteome of the Tibellus oblongus spider unveil molecular diversity of polypeptide toxins

ABSTRACT: The Tibellus genus spider is an active hunter that does not spin webs and remains highly underinvestigated in terms of the venom composition. Here, we present a combination of venom glands transcriptome cDNA analysis, venom proteome analysis for unveiling of the Tibellus genus spider venom composition.

INSTRUMENT(S): LTQ Orbitrap Elite

ORGANISM(S): Tibellus Oblongus

TISSUE(S): Venom

SUBMITTER: Anna Lobas

LAB HEAD: Mikhail V. Gorshkov

PROVIDER: PXD040219 | Pride | 2023-10-23

REPOSITORIES: Pride

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Project description:Spider venoms are a unique source of bioactive peptides displaying remarkable structural stability and potent neuroactivity. Phoneutria nigriventer, often referred to as Brazilian wandering spider, banana spider or “armed” spider, is endemic from South America and amongst the most dangerous venomous spiders in the world. Envenomation accidents with P. nigriventer often occur in Brazil with approximately 4,000 cases per year and which symptoms include priapism, hypertension, blurred vision, sweating, and vomiting, amongst others. Besides its clinical relevance, P. nigriventer venom comprises promising peptide drug leads providing therapeutic effects in a range of disease models. In this study, we further explored the neuroactivity and molecular diversity of the venom from P. nigriventer using fractionation-guided high-throughput cellular assays coupled to proteomics analysis and multi-pharmacology activity to broaden the knowledge and therapeutic potential of this venom, as well as a proof-of-concept for an investigative pipeline to study spider-venom derived neuroactive peptides. We applied ion channel assays in a neuroblastoma cell line to investigate modulation of voltage-gated sodium and calcium channels, and nicotinic acetylcholine α7 receptor. We then investigated the venom components using mass spectrometry to identify peptide masses and sequences associated to the observed neuromodulations. Our findings showed this venom is highly complex compared to other neurotoxin-rich venoms and comprises potent modulators of voltage-gated sodium and calcium channels which were classified into 4 families of neuroactive peptides based on their activities and structures. In addition to the reported P. nigriventer neuroactive peptides, we identified at least 27 novel cysteine-rich venom peptides in which neuroactivities are still to be elucidated in voltage-gated ion channels and other potential targets. Our findings provide a new basis for studying non-explored bioactivities of known and novel neuroactive components in P. nigriventer venom, and further supports the successful application of our discovery pipeline for identifying ion channel-targeting venom peptides with potential to become drug leads with diverse exploratory and therapeutic applications.

			Action	DRS
	checksum.txt	Txt
	venom-Asp-N-05.pep.xml	Pepxml
	venom-Asp-N-05.raw	Raw
	venom-Asp-N-12.pep.xml	Pepxml
	venom-Asp-N-12.raw	Raw

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Venom gland transcriptome and venom proteome of the Tibellus oblongus spider unveil molecular diversity of polypeptide toxins

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