Proteogenomic Assessment of Intraspecific Venom Variability: Molecular Adaptations in the Venom Arsenal of Conus purpurascens.
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ABSTRACT:
SUBMITTER: Grandal M
PROVIDER: S-EPMC8260871 | biostudies-literature |
REPOSITORIES: biostudies-literature
Similar Datasets
Project description:Instraspecific venomics of Conus purpurascens. We employ a functional proteogenomic approach to maximize conopeptide identification from the injected venom of Conus purpurascens.
2020-05-29 | MSV000085498 | MassIVE
Project description:Milked venom from cone snails represent a novel biological resource with a proven track record for drug discovery. To strengthen this correlation, we undertook a chromatographic and mass spectrometric study of individual milked venoms from Conus purpurascens. Milked venoms demonstrate extensive peptide differentiation amongst individual specimens and during captivity. Individual snails were found to lack a consistent set of described conopeptides, but instead demonstrated the ability to change venom expression, composition and post-translational modification incorporation; all variations contribute to an increase in chemical diversity and prey targeting strategies. Quantitative amino acid analysis revealed that milked venom peptides are expressed at ranges up to 3.51-121.01 μM within single milked venom samples. This provides for a 6.37-20,965 fold-excess of toxin to induce apparent IC₅₀ for individual conopeptides identified in this study. Comparative molecular mass analysis of duct venom, milked venom and radula tooth extracts from single C. purpurascens specimens demonstrated a level of peptide continuity. Numerous highly abundant and unique conopeptides remain to be characterized. This study strengthens the notion that approaches in conopeptide drug lead discovery programs will potentially benefit from a greater understanding of the toxinological nature of the milked venoms of Conus.
| S-EPMC3565753 | biostudies-literature
Project description:Cone snail venoms have separately evolved for predation and defense. Despite remarkable inter- and intra-species variability, defined sets of synergistic venom peptides (cabals) are considered essential for prey capture by cone snails. To better understand the role of predatory cabals in cone snails, we used a high-throughput proteomic data mining and visualisation approach. Using this approach, the relationship between the predatory venom peptides from nine C. purpurascens was systematically analysed. Surprisingly, potentially synergistic levels of κ-PVIIA and δ-PVIA were only identified in five of nine specimens. In contrast, the remaining four specimens lacked significant levels of these known excitotoxins and instead contained high levels of the muscle nAChR blockers ψ-PIIIE and αA-PIVA. Interestingly, one of nine specimens expressed both cabals, suggesting that these sub-groups might represent inter-breeding sub-species of C. purpurascens. High throughput cluster analysis also revealed these two cabals clustered with distinct groups of venom peptides that are presently uncharacterised. This is the first report showing that the cone snails of the same species can deploy two separate and distinct predatory cabals for prey capture and shows that the cabals deployed by this species can be more complex than presently realized. Our semi-automated proteomic analysis facilitates the deconvolution of complex venoms to identify co-evolved families of peptides and help unravel their evolutionary relationships in complex venoms.
| S-EPMC5762640 | biostudies-literature
Project description:Elucidating the molecular mechanisms underlying snake venom variability provides important clues for understanding how the biological functions of this powerful toxic arsenal evolve. We analyzed in detail individual transcripts and venom protein isoforms produced by five specimens of a venomous snake (Bothrops atrox) from two nearby but genetically distinct populations from the Brazilian Amazon rainforest which show functional similarities in venom properties. Individual variation was observed among the venoms of these specimens, but the overall abundance of each general toxin family was conserved both in transcript and in venom protein levels. However, when expression of independent paralogues was analyzed, remarkable differences were observed within and among each toxin group, both between individuals and between populations. Transcripts for functionally essential venom proteins (“core function” proteins) were highly expressed in all specimens and showed similar transcription/translation rates. In contrast, other paralogues (“adaptive” proteins) showed lower expression levels and the toxins they coded for varied among different individuals. These results provide support for the inferences that (a) expression and translational differences play a greater role in defining adaptive variation in venom phenotypes than does sequence variation in protein coding genes and (b) convergent adaptive venom phenotypes can be generated through different molecular mechanisms. Significance: Analysis of individual transcripts and venom protein isoforms produced by specimens of a venomous snake (Bothrops atrox), from the Brazilian Amazon rainforest, revealed that transcriptional and translational mechanisms contribute to venom phenotypic variation. Our finding of evidence for high expression of toxin proteins with conserved function supports the hypothesis that the venom phenotype consists of two kinds of proteins: conserved “core function” proteins that provide essential functional activities with broader relevance and less conserved “adaptive” proteins that vary in expression and may permit customization of protein function. These observations allowed us to suggest that genetic mechanisms controlling venom variability are not restricted to selection of gene copies or mutations in structural genes but also to selection of the mechanisms controlling gene expression, contributing to the plasticity of this important phenotype for venomous snakes.
2023-07-04 | PXD043541 | Pride
Project description:Conotoxins constitute a treasury of drug resources and have attracted widespread attention. In order to explore biological candidates from the marine cone snail, we isolated and identified three novel conopeptides named as Vi14b, Vi002, Vi003, three conotoxin variants named as Mr3d.1, Mr3e.1, Tx3a.1, and three known conotoxins (Vi15a, Mr3.8 and TCP) from crude venoms of Conus virgo, Conus marmoreus and Conus texile. Mr3.8 (I-V, II-VI, III-IV) and Tx3a.1 (I-III, II-VI, IV-V) both showed a novel pattern of disulfide connectivity, different from that previously established for the µ- and ψ-conotoxins. Concerning the effect on voltage-gated sodium channels, Mr3e.1, Mr3.8, Tx3a.1, TCP inhibited Nav1.4 or Nav1.8 by 21.51~24.32% of currents at semi-activated state (TP2) at 10 μmol/L. Certain anti-ovarian cancer effects on ID-8 cells were exhibited by Tx3a.1, Mr3e.1 and Vi14b with IC50 values of 24.29 µM, 54.97 µM and 111.6 µM, respectively. This work highlights the role of conotoxin libraries in subsequent drug discovery for ovarian cancer treatment.
| S-EPMC9573077 | biostudies-literature
Project description:The piscivorous cone snail Conus tulipa has evolved a net-hunting strategy, akin to the deadly Conus geographus, and is considered the second most dangerous cone snail to humans. Here, we present the first venomics study of C. tulipa venom using integrated transcriptomic and proteomic approaches. Parallel transcriptomic analysis of two C. tulipa specimens revealed striking differences in conopeptide expression levels (2.5-fold) between individuals, identifying 522 and 328 conotoxin precursors from 18 known gene superfamilies. Despite broad overlap at the superfamily level, only 86 precursors (11%) were common to both specimens. Conantokins (NMDA antagonists) from the superfamily B1 dominated the transcriptome and proteome of C. tulipa venom, along with superfamilies B2, A, O1, O3, con-ikot-ikot and conopressins, plus novel putative conotoxins precursors T1.3, T6.2, T6.3, T6.4 and T8.1. Thus, C. tulipa venom comprised both paralytic (putative ion channel modulating ?-, ?-, ?-, ?-) and non-paralytic (conantokins, con-ikot-ikots, conopressins) conotoxins. This venomic study confirms the potential for non-paralytic conotoxins to contribute to the net-hunting strategy of C. tulipa.
| S-EPMC6356538 | biostudies-literature
Project description:Observations of the mollusc-hunting cone snail Conus textile during feeding reveal that prey are often stung multiple times in succession. While studies on the venom peptides injected by fish-hunting cone snails have become common, these approaches have not been widely applied to the analysis of the injected venoms from mollusc-hunters. We have successfully obtained multiple injected venom samples from C. textile individuals, allowing us to investigate venom compositional variation during prey capture. Our studies indicate that C. textile individuals alter the composition of prey-injected venom peptides during single feeding events. The qualitative results obtained by MALDI-ToF mass spectrometry are mirrored by quantitative changes in venom composition observed by reverse-phase high performance liquid chromatography. While it is unclear why mollusc-hunting cone snails inject prey multiple times prior to engulfment, our study establishes for the first time a link between this behavior and compositional changes of the venom during prey capture. Changes in venom composition during hunting may represent a multi-step strategy utilized by these venomous animals to slow and incapacitate prey prior to engulfment.
| S-EPMC4062396 | biostudies-literature
Project description:BackgroundThe venomous marine gastropods, cone snails (genus Conus), inject prey with a lethal cocktail of conopeptides, small cysteine-rich peptides, each with a high affinity for its molecular target, generally an ion channel, receptor or transporter. Over the last decade, conopeptides have proven indispensable reagents for the study of vertebrate neurotransmission. Conus bullatus belongs to a clade of Conus species called Textilia, whose pharmacology is still poorly characterized. Thus the genomics analyses presented here provide the first step toward a better understanding the enigmatic Textilia clade.ResultsWe have carried out a sequencing survey of the Conus bullatus genome and venom-duct transcriptome. We find that conopeptides are highly expressed within the venom-duct, and describe an in silico pipeline for their discovery and characterization using RNA-seq data. We have also carried out low-coverage shotgun sequencing of the genome, and have used these data to determine its size, genome-wide base composition, simple repeat, and mobile element densities.ConclusionsOur results provide the first global view of venom-duct transcription in any cone snail. A notable feature of Conus bullatus venoms is the breadth of A-superfamily peptides expressed in the venom duct, which are unprecedented in their structural diversity. We also find SNP rates within conopeptides are higher compared to the remainder of C. bullatus transcriptome, consistent with the hypothesis that conopeptides are under diversifying selection.
| S-EPMC3040727 | biostudies-literature
Project description:Cone snails, genus Conus, are predatory marine snails that use venom to capture their prey. This venom contains a diverse array of peptide toxins, known as conotoxins, which undergo a diverse set of posttranslational modifications. Amidating enzymes modify peptides and proteins containing a C-terminal glycine residue, resulting in loss of the glycine residue and amidation of the preceding residue. A significant fraction of peptides present in the venom of cone snails contain C-terminal amidated residues, which are important for optimizing biological activity. This study describes the characterization of the amidating enzyme, peptidylglycine α-amidating monooxygenase (PAM), present in the venom duct of cone snails, Conus bullatus and Conus geographus. PAM is known to carry out two functions, peptidyl α-hydroxylating monooxygenase (PHM) and peptidylamido-glycolate lyase (PAL). In some animals, such as Drosophila melanogaster, these two functions are present in separate polypeptides, working as individual enzymes. In other animals, such as mammals and in Aplysia californica, PAM activity resides in a single, bifunctional polypeptide. Using specific oligonucleotide primers and reverse transcription-polymerase chain reaction we have identified and cloned from the venom duct cDNA library, a cDNA with 49% homology to PAM from A. californica. We have determined that both the PHM and PAL activities are encoded in one mRNA polynucleotide in both C. bullatus and C. geographus. We have directly demonstrated enzymatic activity catalyzing the conversion of dansyl-YVG-COOH to dansyl-YV-NH2 in cloned cDNA expressed in Drosophila S2 cells.
| S-EPMC4286251 | biostudies-literature
Project description:The fish-hunting cone snail, Conus geographus, is the deadliest snail on earth. In the absence of medical intervention, 70% of human stinging cases are fatal. Although, its venom is known to consist of a cocktail of small peptides targeting different ion-channels and receptors, the bulk of its venom constituents, their sites of manufacture, relative abundances and how they function collectively in envenomation has remained unknown.We have used transcriptome sequencing to systematically elucidate the contents the C. geographus venom duct, dividing it into four segments in order to investigate each segment's mRNA contents. Three different types of calcium channel (each targeted by unrelated, entirely distinct venom peptides) and at least two different nicotinic receptors appear to be targeted by the venom. Moreover, the most highly expressed venom component is not paralytic, but causes sensory disorientation and is expressed in a different segment of the venom duct from venoms believed to cause sensory disruption. We have also identified several new toxins of interest for pharmaceutical and neuroscience research.Conus geographus is believed to prey on fish hiding in reef crevices at night. Our data suggest that disorientation of prey is central to its envenomation strategy. Furthermore, venom expression profiles also suggest a sophisticated layering of venom-expression patterns within the venom duct, with disorientating and paralytic venoms expressed in different regions. Thus, our transcriptome analysis provides a new physiological framework for understanding the molecular envenomation strategy of this deadly snail.
| S-EPMC3441800 | biostudies-literature