Dataset Information

Paulistine--The Functional Duality of a Wasp Venom Peptide Toxin.

ABSTRACT: It has been reported that Paulistine in the venom of the wasp Polybia paulista co-exists as two different forms: an oxidized form presenting a compact structure due to the presence of a disulfide bridge, which causes inflammation through an apparent interaction with receptors in the 5-lipoxygenase pathway, and a naturally reduced form (without the disulfide bridge) that exists in a linear conformation and which also causes hyperalgesia and acts in the cyclooxygenase type II pathway. The reduced peptide was acetamidomethylated (Acm-Paulistine) to stabilize this form, and it still maintained its typical inflammatory activity. Oxidized Paulistine docks onto PGHS2 (COX-2) molecules, blocking the access of oxygen to the heme group and inhibiting the inflammatory activity of Acm-Paulistine in the cyclooxygenase type II pathway. Docking simulations revealed that the site of the docking of Paulistine within the PGHS2 molecule is unusual among commercial inhibitors of the enzyme, with an affinity potentially much higher than those observed for traditional anti-inflammatory drugs. Therefore, Paulistine causes inflammatory activity at the level of the 5-lipooxygenase pathway and, in parallel, it competes with its reduced form in relation to the activation of the cyclooxygenase pathway. Thus, while the reduced Paulistine causes inflammation, its oxidized form is a potent inhibitor of this activity.

SUBMITTER: Arcuri HA

PROVIDER: S-EPMC4810206 | biostudies-literature | 2016 Feb

REPOSITORIES: biostudies-literature

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Paulistine--The Functional Duality of a Wasp Venom Peptide Toxin.

Arcuri Helen Andrade HA Gomes Paulo Cesar PC de Souza Bibiana Monson BM Dias Nathalia Baptista NB Brigatte Patrícia P Stabeli Rodrigo Guerino RG Palma Mario Sergio MS

Toxins 20160229 3

It has been reported that Paulistine in the venom of the wasp Polybia paulista co-exists as two different forms: an oxidized form presenting a compact structure due to the presence of a disulfide bridge, which causes inflammation through an apparent interaction with receptors in the 5-lipoxygenase pathway, and a naturally reduced form (without the disulfide bridge) that exists in a linear conformation and which also causes hyperalgesia and acts in the cyclooxygenase type II pathway. The reduced ...[more]

PMID: 26938560

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Project description:Background The generalist dipteran pupal parasitoid Nasonia vitripennis injects 79 venom peptides into the host before egg laying. This venom induces several important changes in the host, including developmental arrest, immunosuppression, and alterations to normal metabolism. It is hoped that diverse and potent bioactivities of N. vitripennis venom provide an opportunity for the design of novel acting drugs. However, currently very little is known about the individual functions of N. vitripennis venom peptides and less than half can be bioinformatically annotated. The paucity of annotation information complicates the design of studies that seek to better understand the potential mechanisms underlying the envenomation response. Although the RNA interference system of N. vitripennis provides an opportunity to functionally characterise venom encoding genes, with 79 candidates this represents a daunting task. For this reason we were interested in determining the expression levels of venom encoding genes in the venom gland, such that this information could be used to rank candidate venoms. To do this we carried out deep sequencing of the transcriptome of the venom gland and neighbouring ovary tissue and used RNA-seq to measure expression from the 79 venom encoding genes. The generation of a specific venom gland transcriptome dataset also provides further opportunities to investigate novel features of this highly specialised organ. Results High throughput sequencing and RNA-seq revealed that the highest expressed venom encoding gene in the venom gland was a serine protease called Nasvi2EG007167, which has previously been implicated in the apoptotic activity of N. vitripennis venom. As expected the RNA-seq confirmed that the N. vitripennis venom encoding genes are almost exclusively expressed in the venom gland relative to the neighbouring ovary tissue. Novel peptides appear to perform key roles in N. vitripennis venom function as only four of the highest 15 expressed venom encoding genes are bioinformatically annotationed. The high throughput sequencing data also provided evidence for the existence of an additional 471 novel genes in the Nasonia genome that are expressed in the venom gland and ovary. Finally, metagenomic analysis of venom gland transcripts identified viral transcripts that may play an important part in the N. vitripennis venom function. Conclusions The expression level information provided here for the 79 venom encoding genes provides an unbiased dataset that can be used by the N. vitripennis community to identify high value candidates for further functional characterisation. These candidates represent bioactive peptides that have value in drug development pipelines.

Dataset Information

Paulistine--The Functional Duality of a Wasp Venom Peptide Toxin.

Publications

Paulistine--The Functional Duality of a Wasp Venom Peptide Toxin.

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