Diversity of Conopeptides and Conoenzymes from the Venom Duct of the Marine Cone Snail Conus bayani as Determined from Transcriptomic and Proteomic Analyses

Marine cone snails are predatory gastropods characterized by a well-developed venom apparatus and highly evolved hunting strategies that utilize toxins to paralyze prey and defend against predators. The venom of each species of cone snail has a large number of pharmacologically active peptides known as conopeptides or conotoxins that are usually unique in each species. Nevertheless, venoms of only very few species have been characterized so far by transcriptomic approaches. In this study, we used transcriptome sequencing technologies and mass spectrometric methods to describe the diversity of venom components expressed by a worm-hunting species, Conus bayani. A total of 82 conotoxin sequences were retrieved from transcriptomic data that contain 54 validated conotoxin sequences clustered into 21 gene superfamilies including divergent gene family, 17 sequences clustered to 6 different conotoxin classes, and 11 conotoxins classified as unassigned gene family. Seven new conotoxin sequences showed unusual cysteine patterns. We were also able to identify 19 peptide sequences using mass spectrometry that completely overlapped with the conotoxin sequences obtained from transcriptome analysis. Importantly, herein we document the presence of 16 proteins that include five post-translational modifying enzymes obtained from transcriptomic data. Our results revealed diverse and novel conopeptides of an unexplored species that could be used extensively in biomedical research due to their therapeutic potentials.

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Pharmacologically Active Peptides and Proteins from Bee Venom

Animal Toxins ◽

10.1007/978-3-0348-8466-2_9 ◽

2000 ◽

pp. 127-151

Author(s):

Peter N. Strong ◽

Jonathan D. F. Wadsworth

Keyword(s):

Bee Venom ◽

Active Peptides ◽

Pharmacologically Active

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Pharmacologically Active Peptides produced in the Tissues of the Host during Chronic Trypanosome Infections

Nature ◽

10.1038/212190b0 ◽

1966 ◽

Vol 212 (5058) ◽

pp. 190-191 ◽

Cited By ~ 13

Author(s):

P. F. L. BOREHAM

Keyword(s):

Active Peptides ◽

Pharmacologically Active

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Identification of Novel Conopeptides and Distinct Gene Superfamilies in the Marine Cone Snail Conus quercinus

Frontiers in Marine Science ◽

10.3389/fmars.2021.766792 ◽

2021 ◽

Vol 8 ◽

Author(s):

Han Zhang ◽

Lei Wang ◽

Xiang Yang ◽

Zhiwei Lian ◽

Yinbin Qiu ◽

...

Keyword(s):

Mass Spectrometry ◽

Prokaryotic Expression ◽

Disulfide Bonds ◽

De Novo ◽

Animal Experiments ◽

Cone Snail ◽

Active Peptides ◽

Neuroscience Research ◽

First Time ◽

Mass Spectrometry Mass Spectrometry

Conopeptides from the marine cone snails are a mixture of cysteine-rich active peptides, representing a unique and fertile resource for neuroscience research and drug discovery. The ConoServer database includes 8,134 conopeptides from 122 Conus species, yet many more natural conopeptides remain to be discovered. Here, we identified 517 distinct conopeptide precursors in Conus quercinus using de novo deep transcriptome sequencing. Ten of these precursors were verified at the protein level using liquid chromatography-mass spectrometry/mass spectrometry (LC-MS/MS). The combined gene and protein analyses revealed two novel gene superfamilies (Que-MNCLQ and Que-MAMNV), and three other gene superfamilies (N, P, and I1) were reported for the first time in C. quercinus. From the Que-MAMNV superfamily, a novel conotoxin, Que-0.1, was obtained via cloning and prokaryotic expression. We also documented a new purification process that can be used to induce the expression of conopeptides containing multiple pairs of disulfide bonds. The animal experiments showed that Que-0.1 strongly inhibited neuroconduction; the effects of Que-1.0 were 6.25 times stronger than those of pethidine hydrochloride. In addition, a new cysteine framework (CC-C-C-C-C-C-CC-C-C-C-C-C) was found in C. quercinus. These discoveries accelerate our understanding of conopeptide diversity in the genus, Conus and supply promising materials for medical research.

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187 Panel discussion of the paper of r. schwyzer : structure-activity relationships among pharmacologically active peptides

Biochemical Pharmacology ◽

10.1016/0006-2952(61)90365-3 ◽

1961 ◽

Vol 8 (1) ◽

pp. 58

Author(s):

R.A. Boissonnas

Keyword(s):

Panel Discussion ◽

Active Peptides ◽

Structure Activity Relationships ◽

Structure Activity ◽

Pharmacologically Active

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Transcriptomic Data Sets To Determine Gene Expression Changes Mediated by the Presence of PBT2 in Growth Medium of Multidrug-Resistant Neisseria gonorrhoeae WHO Z

Microbiology Resource Announcements ◽

10.1128/mra.00283-20 ◽

2020 ◽

Vol 9 (21) ◽

Author(s):

Freda E.-C. Jen ◽

Ibrahim M. El-Deeb ◽

John M. Atack ◽

Mark von Itzstein ◽

Michael P. Jennings

Keyword(s):

Neisseria Gonorrhoeae ◽

Transcriptome Sequencing ◽

Multidrug Resistant ◽

Data Sets ◽

Sequencing Data ◽

Transmitted Infection ◽

High Coverage ◽

Content Type ◽

Sexually Transmitted ◽

Transcriptomic Data

ABSTRACT Neisseria gonorrhoeae causes the sexually transmitted infection gonorrhea. High-coverage (∼3,300-fold) transcriptome sequencing data have been collected from multidrug-resistant N. gonorrhoeae strain WHO Z grown in the presence and absence of PBT2.

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The PARA-suite: PAR-CLIP specific sequence read simulation and processing

PeerJ ◽

10.7717/peerj.2619 ◽

2016 ◽

Vol 4 ◽

pp. e2619 ◽

Cited By ~ 8

Author(s):

Andreas Kloetgen ◽

Arndt Borkhardt ◽

Jessica I. Hoell ◽

Alice C. McHardy

Keyword(s):

Binding Site ◽

Transcriptome Sequencing ◽

Detection Accuracy ◽

Rna Seq ◽

Specific Sequence ◽

Read Alignment ◽

Detection Algorithms ◽

Sequencing Technologies ◽

A Genome ◽

Wide Scale

BackgroundNext-generation sequencing technologies have profoundly impacted biology over recent years. Experimental protocols, such as photoactivatable ribonucleoside-enhanced cross-linking and immunoprecipitation (PAR-CLIP), which identifies protein–RNA interactions on a genome-wide scale, commonly employ deep sequencing. With PAR-CLIP, the incorporation of photoactivatable nucleosides into nascent transcripts leads to high rates of specific nucleotide conversions during reverse transcription. So far, the specific properties of PAR-CLIP-derived sequencing reads have not been assessed in depth.MethodsWe here compared PAR-CLIP sequencing reads to regular transcriptome sequencing reads (RNA-Seq) to identify distinctive properties that are relevant for reference-based read alignment of PAR-CLIP datasets. We developed a set of freely available tools for PAR-CLIP data analysis, called the PAR-CLIP analyzer suite (PARA-suite). The PARA-suite includes error model inference, PAR-CLIP read simulation based on PAR-CLIP specific properties, a full read alignment pipeline with a modified Burrows–Wheeler Aligner algorithm and CLIP read clustering for binding site detection.ResultsWe show that differences in the error profiles of PAR-CLIP reads relative to regular transcriptome sequencing reads (RNA-Seq) make a distinct processing advantageous. We examine the alignment accuracy of commonly applied read aligners on 10 simulated PAR-CLIP datasets using different parameter settings and identified the most accurate setup among those read aligners. We demonstrate the performance of the PARA-suite in conjunction with different binding site detection algorithms on several real PAR-CLIP and HITS-CLIP datasets. Our processing pipeline allowed the improvement of both alignment and binding site detection accuracy.AvailabilityThe PARA-suite toolkit and the PARA-suite aligner are available athttps://github.com/akloetgen/PARA-suiteandhttps://github.com/akloetgen/PARA-suite_aligner, respectively, under the GNU GPLv3 license.

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The odorant-binding proteins of Drosophila melanogaster : annotation and characterization of a divergent gene family

Gene ◽

10.1016/s0378-1119(02)00672-8 ◽

2002 ◽

Vol 292 (1-2) ◽

pp. 43-55 ◽

Cited By ~ 71

Author(s):

Laurie A Graham ◽

Peter L Davies

Keyword(s):

Drosophila Melanogaster ◽

Gene Family ◽

Binding Proteins ◽

Odorant Binding Proteins ◽

Divergent Gene ◽

Odorant Binding

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Small-molecule mimicry hunting strategy in the imperial cone snail, Conus imperialis

Science Advances ◽

10.1126/sciadv.abf2704 ◽

2021 ◽

Vol 7 (11) ◽

pp. eabf2704

Author(s):

Joshua P. Torres ◽

Zhenjian Lin ◽

Maren Watkins ◽

Paula Flórez Salcedo ◽

Robert P. Baskin ◽

...

Keyword(s):

Small Molecules ◽

Bioactive Peptides ◽

Cone Snail ◽

Fake News ◽

Specialized Metabolites ◽

Hunting Strategies ◽

Venomous Animals ◽

Platynereis Dumerilii ◽

Species Specific ◽

Hunting Strategy

Venomous animals hunt using bioactive peptides, but relatively little is known about venom small molecules and the resulting complex hunting behaviors. Here, we explored the specialized metabolites from the venom of the worm-hunting cone snail, Conus imperialis. Using the model polychaete worm Platynereis dumerilii, we demonstrate that C. imperialis venom contains small molecules that mimic natural polychaete mating pheromones, evoking the mating phenotype in worms. The specialized metabolites from different cone snails are species-specific and structurally diverse, suggesting that the cones may adopt many different prey-hunting strategies enabled by small molecules. Predators sometimes attract prey using the prey’s own pheromones, in a strategy known as aggressive mimicry. Instead, C. imperialis uses metabolically stable mimics of those pheromones, indicating that, in biological mimicry, even the molecules themselves may be disguised, providing a twist on fake news in chemical ecology.

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