14 results on '"Cone snail"'
Search Results
2. Venom Diversity and Evolution in the Most Divergent Cone Snail Genus Profundiconus .
- Author
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Fassio G, Modica MV, Mary L, Zaharias P, Fedosov AE, Gorson J, Kantor YI, Holford M, and Puillandre N
- Subjects
- Animals, Biological Evolution, Conotoxins genetics, Conotoxins toxicity, Conus Snail chemistry, Conus Snail genetics, Genetic Variation
- Abstract
Profundiconus is the most divergent cone snail genus and its unique phylogenetic position, sister to the rest of the family Conidae, makes it a key taxon for examining venom evolution and diversity. Venom gland and foot transcriptomes of Profundiconus cf. vaubani and Profundiconus neocaledonicus were de novo assembled, annotated, and analyzed for differential expression. One hundred and thirty-seven venom components were identified from P. cf. vaubani , with only four shared by both species. The majority of the transcript diversity was composed of putative peptides, including conotoxins, profunditoxins, turripeptides, insulin, and prohormone-4. However, there were also a significant percentage of other putative venom components such as chymotrypsin and L-rhamnose-binding lectin. The large majority of conotoxins appeared to be from new gene superfamilies, three of which are highly different from previously reported venom peptide toxins. Their low conotoxin diversity and the type of insulin found suggested that these species, for which no ecological information are available, have a worm or molluscan diet associated with a narrow dietary breadth. Our results indicate that P. neocaledonicus venom is highly distinct from that of other cone snails, and therefore important for examining venom evolution in the Conidae family.Profundiconus venom is highly distinct from that of other cone snails, and therefore important for examining venom evolution in the Conidae family.
- Published
- 2019
- Full Text
- View/download PDF
3. A Novel Dimeric Conotoxin, FrXXA, from the Vermivorous Cone Snail
- Author
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Ximena C, Rodriguez-Ruiz, Manuel B, Aguilar, Mónica A, Ortíz-Arellano, Helena, Safavi-Hemami, and Estuardo, López-Vera
- Subjects
Mice ,Snails ,Conus Snail ,Animals ,Amino Acid Sequence ,Nicotinic Antagonists ,Receptors, Nicotinic ,Conotoxins - Abstract
We isolated a new dimeric conotoxin with inhibitory activity against neuronal nicotinic acetylcholine receptors. Edman degradation and transcriptomic studies indicate a homodimeric conotoxin composed by two chains of 47 amino acid in length. It has the cysteine framework XX and 10 disulfide bonds. According to conotoxin nomenclature, it has been named as αD-FrXXA. The αD-FrXXA conotoxin inhibited the ACh-induced response on nAChR with a IC
- Published
- 2022
4. Cone Snails: A Big Store of Conotoxins for Novel Drug Discovery.
- Author
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Gao B, Peng C, Yang J, Yi Y, Zhang J, and Shi Q
- Subjects
- Animals, Conotoxins genetics, Conotoxins metabolism, Conus Snail classification, Humans, Protein Binding, Protein Conformation, Proteome, Receptors, Nicotinic metabolism, Species Specificity, Transcriptome, Conotoxins isolation & purification, Conus Snail chemistry, Drug Discovery methods
- Abstract
Marine drugs have developed rapidly in recent decades. Cone snails, a group of more than 700 species, have always been one of the focuses for new drug discovery. These venomous snails capture prey using a diverse array of unique bioactive neurotoxins, usually named as conotoxins or conopeptides. These conotoxins have proven to be valuable pharmacological probes and potential drugs due to their high specificity and affinity to ion channels, receptors, and transporters in the nervous systems of target prey and humans. Several research groups, including ours, have examined the venom gland of cone snails using a combination of transcriptomic and proteomic sequencing, and revealed the existence of hundreds of conotoxin transcripts and thousands of conopeptides in each Conus species. Over 2000 nucleotide and 8000 peptide sequences of conotoxins have been published, and the number is still increasing quickly. However, more than 98% of these sequences still lack 3D structural and functional information. With the rapid development of genomics and bioinformatics in recent years, functional predictions and investigations on conotoxins are making great progress in promoting the discovery of novel drugs. For example, ω-MVIIA was approved by the U.S. Food and Drug Administration in 2004 to treat chronic pain, and nine more conotoxins are at various stages of preclinical or clinical evaluation. In short, the genus Conus , the big family of cone snails, has become an important genetic resource for conotoxin identification and drug development.
- Published
- 2017
- Full Text
- View/download PDF
5. Predatory and Defensive Strategies in Cone Snails.
- Author
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Ratibou Z, Inguimbert N, and Dutertre S
- Subjects
- Humans, Animals, Mollusk Venoms chemistry, Peptides, Venoms, Snails, Conotoxins toxicity, Conotoxins chemistry, Conus Snail chemistry
- Abstract
Cone snails are carnivorous marine animals that prey on fish (piscivorous), worms (vermivorous), or other mollusks (molluscivorous). They produce a complex venom mostly made of disulfide-rich conotoxins and conopeptides in a compartmentalized venom gland. The pharmacology of cone snail venom has been increasingly investigated over more than half a century. The rising interest in cone snails was initiated by the surprising high human lethality rate caused by the defensive stings of some species. Although a vast amount of information has been uncovered on their venom composition, pharmacological targets, and mode of action of conotoxins, the venom-ecology relationships are still poorly understood for many lineages. This is especially important given the relatively recent discovery that some species can use different venoms to achieve rapid prey capture and efficient deterrence of aggressors. Indeed, via an unknown mechanism, only a selected subset of conotoxins is injected depending on the intended purpose. Some of these remarkable venom variations have been characterized, often using a combination of mass spectrometry and transcriptomic methods. In this review, we present the current knowledge on such specific predatory and defensive venoms gathered from sixteen different cone snail species that belong to eight subgenera: Pionoconus , Chelyconus , Gastridium , Cylinder , Conus , Stephanoconus , Rhizoconus , and Vituliconus . Further studies are needed to help close the gap in our understanding of the evolved ecological roles of many cone snail venom peptides.
- Published
- 2024
- Full Text
- View/download PDF
6. Conotoxin Prediction: New Features to Increase Prediction Accuracy.
- Author
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Monroe LK, Truong DP, Miner JC, Adikari SH, Sasiene ZJ, Fenimore PW, Alexandrov B, Williams RF, and Nguyen HB
- Subjects
- Animals, Amino Acid Sequence, Peptides chemistry, Cysteine metabolism, Disulfides, Conotoxins chemistry, Conus Snail chemistry
- Abstract
Conotoxins are toxic, disulfide-bond-rich peptides from cone snail venom that target a wide range of receptors and ion channels with multiple pathophysiological effects. Conotoxins have extraordinary potential for medical therapeutics that include cancer, microbial infections, epilepsy, autoimmune diseases, neurological conditions, and cardiovascular disorders. Despite the potential for these compounds in novel therapeutic treatment development, the process of identifying and characterizing the toxicities of conotoxins is difficult, costly, and time-consuming. This challenge requires a series of diverse, complex, and labor-intensive biological, toxicological, and analytical techniques for effective characterization. While recent attempts, using machine learning based solely on primary amino acid sequences to predict biological toxins (e.g., conotoxins and animal venoms), have improved toxin identification, these methods are limited due to peptide conformational flexibility and the high frequency of cysteines present in toxin sequences. This results in an enumerable set of disulfide-bridged foldamers with different conformations of the same primary amino acid sequence that affect function and toxicity levels. Consequently, a given peptide may be toxic when its cysteine residues form a particular disulfide-bond pattern, while alternative bonding patterns (isoforms) or its reduced form (free cysteines with no disulfide bridges) may have little or no toxicological effects. Similarly, the same disulfide-bond pattern may be possible for other peptide sequences and result in different conformations that all exhibit varying toxicities to the same receptor or to different receptors. We present here new features, when combined with primary sequence features to train machine learning algorithms to predict conotoxins, that significantly increase prediction accuracy.
- Published
- 2023
- Full Text
- View/download PDF
7. Nuclear Magnetic Resonance seq (NMRseq): A New Approach to Peptide Sequence Tags
- Author
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Norelle L. Daly and David Wilson
- Subjects
0301 basic medicine ,Magnetic Resonance Spectroscopy ,Health, Toxicology and Mutagenesis ,lcsh:Medicine ,Peptide ,Toxicology ,Article ,Cone snail ,03 medical and health sciences ,Nuclear magnetic resonance ,NMR spectroscopy ,Sequence Analysis, Protein ,Animals ,disulfide-rich peptide ,Conotoxin ,Amino Acid Sequence ,Peptide sequence ,Sequence (medicine) ,chemistry.chemical_classification ,Conus geographus ,biology ,Chemistry ,lcsh:R ,Conus Snail ,Nuclear magnetic resonance spectroscopy ,biology.organism_classification ,NMR spectra database ,030104 developmental biology ,conotoxin ,Conotoxins ,Peptides - Abstract
Structural analysis of peptides with nuclear magnetic resonance (NMR) spectroscopy generally relies on knowledge of the primary sequence to enable assignment of the resonances prior to determination of the three-dimensional structure. Resonance assignment without knowledge of the sequence is complicated by redundancy in amino acid type, making complete de novo sequencing using NMR spectroscopy unlikely to be feasible. Despite this redundancy, we show here that NMR spectroscopy can be used to identify short sequence tags that can be used to elucidate full-length peptide sequences via database searching. In the current study, we have used this approach to identify conotoxins from the venom of the cone snail Conus geographus and determined the three-dimensional structure of a member of the I3 superfamily. This approach is most likely to be useful for the characterization of disulfide-rich peptides, such as those that were chosen for this study, as they generally have well-defined structures, which enhances the quality of the NMR spectra. In contrast to other sequencing methods, the lack of sample manipulation, such as protease digestion, allows for subsequent bioassays to be carried out using the native sample used for sequence identification.
- Published
- 2018
- Full Text
- View/download PDF
8. αD-Conotoxins in Species of the Eastern Pacific: The Case of Conus princeps from Mexico
- Author
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Víctor Landa-Jaime, Arisaí C Hernández-Sámano, Cesar Vicente Ferreira Batista, Estuardo López-Vera, Andrés Falcón, Manuel B. Aguilar, Fernando Z. Zamudio, Michael C. Jeziorski, and Jesús Emilio Michel-Morfín
- Subjects
animal structures ,Health, Toxicology and Mutagenesis ,lcsh:Medicine ,Peptide ,Venom ,hα3β2 nAChR ,hα7 nAChR ,nAChR ,Receptors, Nicotinic ,Toxicology ,complex mixtures ,Article ,Cone snail ,03 medical and health sciences ,Xenopus laevis ,0302 clinical medicine ,parasitic diseases ,Conus ,medicine ,Animals ,Conotoxin ,Amino Acid Sequence ,Conus princeps ,Mexico ,030304 developmental biology ,chemistry.chemical_classification ,0303 health sciences ,αD-conotoxin ,Edman degradation ,biology ,lcsh:R ,fungi ,Conus Snail ,biology.organism_classification ,Molecular biology ,Nicotinic acetylcholine receptor ,chemistry ,Oocytes ,Female ,Conotoxins ,Peptides ,030217 neurology & neurosurgery ,Acetylcholine ,medicine.drug - Abstract
Conus snails produce venoms containing numerous peptides such as the &alpha, conotoxins (&alpha, CTXs), which are well-known nicotinic acetylcholine receptor (nAChR) antagonists. Thirty-eight chromatographic fractions from Conus princeps venom extract were isolated by RP-HPLC. The biological activities of 37 fractions (0.07 µ, g/µ, L) were assayed by two-electrode voltage clamp on human &alpha, 7 nAChRs expressed in Xenopus laevis oocytes. Fractions F7 and F16 notably inhibited the response elicited by acetylcholine by 52.7 ±, 15.2% and 59.6 ±, 2.5%, respectively. Fraction F7 was purified, and an active peptide (F7-3) was isolated. Using a combination of Edman degradation, mass spectrometry, and RNASeq, we determined the sequence of peptide F7-3: AVKKTCIRSTOGSNWGRCCLTKMCHTLCCARSDCTCVYRSGKGHGCSCTS, with one hydroxyproline (O) and a free C-terminus. The average mass of this peptide, 10,735.54 Da, indicates that it is a homodimer of identical subunits, with 10 disulfide bonds in total. This peptide is clearly similar to &alpha, D-CTXs from species of the Indo-Pacific. Therefore, we called it &alpha, D-PiXXA. This toxin slowly and reversibly inhibited the ACh-induced response of the h&alpha, 7 nAChR subtype, with an IC50 of 6.2 &mu, M, and it does not affect the h&alpha, 3&beta, 2 subtype at 6.5 &mu, M.
- Published
- 2019
9. A New Member of Gamma-Conotoxin Family Isolated from Conus princeps Displays a Novel Molecular Target
- Author
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Jesús Noda Ferro, Luis Javier González, Emilio Salceda, Enrique Soto, Samanta Jiménez, Alexei F. Licea-Navarro, Daniela Chávez, Manuel B. Aguilar, and Johanna Bernáldez
- Subjects
Male ,0301 basic medicine ,Health, Toxicology and Mutagenesis ,Molecular Sequence Data ,lcsh:Medicine ,Peptide ,Biology ,Toxicology ,Article ,Cone snail ,03 medical and health sciences ,0302 clinical medicine ,dorsal root ganglion neurons ,Ganglia, Spinal ,Conus ,Animals ,Rats, Long-Evans ,Amino Acid Sequence ,Conotoxin ,Peptide sequence ,mass spectrometry ,Neurons ,chemistry.chemical_classification ,gamma-conotoxin ,Conus princeps ,calcium channel ,Edman degradation ,lcsh:R ,Conus Snail ,biology.organism_classification ,Amino acid ,030104 developmental biology ,Biochemistry ,chemistry ,Female ,Calcium Channels ,Conotoxins ,Peptides ,030217 neurology & neurosurgery - Abstract
A novel conotoxin, named as PiVIIA, was isolated from the venom of Conus princeps, a marine predatory cone snail collected in the Pacific Southern Coast of Mexico. Chymotryptic digest of the S-alkylated peptide in combination with liquid chromatography coupled to tandem mass spectrometry, were used to define the sequencing of this peptide. Eleven N-terminal amino acids were verified by automated Edman degradation. PiVIIA is a 25-mer peptide (CDAOTHYCTNYWγCCSGYCγHSHCW) with six cysteine residues forming three disulphide bonds, a hydroxyproline (O) and two gamma carboxyglutamic acid (γ) residues. Based on the arrangement of six Cys residues (C-C-CC-C-C), this conotoxin might belong to the O2-superfamily. Moreover, PiVIIA has a conserved motif (-γCCS-) that characterizes γ-conotoxins from molluscivorous Conus. Peptide PiVIIA has 45% sequence identity with γ-PnVIIA-the prototype of this family. Biological activity of PiVIIA was assessed by voltage-clamp recording in rat dorsal root ganglion neurons. Perfusion of PiVIIA in the µM range produces a significant increase in the Ca(2+) currents, without significantly modifying the Na⁺, K⁺ or proton-gated acid sensing ionic currents. These results indicate that PiVIIA is a new conotoxin whose activity deserves further studies to define its potential use as a positive modulator of neuronal activity.
- Published
- 2016
10. Cone Snails: A Big Store of Conotoxins for Novel Drug Discovery
- Author
-
Bingmiao Gao, Junqing Zhang, Qiong Shi, Jiaan Yang, Peng Chao, and Yunhai Yi
- Subjects
0301 basic medicine ,Research groups ,Proteome ,Protein Conformation ,Health, Toxicology and Mutagenesis ,lcsh:Medicine ,Genomics ,Review ,Computational biology ,Receptors, Nicotinic ,Toxicology ,complex mixtures ,Cone snail ,Food and drug administration ,03 medical and health sciences ,0302 clinical medicine ,Species Specificity ,Drug Discovery ,Conus ,Animals ,Humans ,Conotoxin ,cone snail ,biology ,Drug discovery ,lcsh:R ,Conus Snail ,biology.organism_classification ,drug development ,030104 developmental biology ,Drug development ,conotoxin ,Conotoxins ,Transcriptome ,030217 neurology & neurosurgery ,Protein Binding - Abstract
Marine drugs have developed rapidly in recent decades. Cone snails, a group of more than 700 species, have always been one of the focuses for new drug discovery. These venomous snails capture prey using a diverse array of unique bioactive neurotoxins, usually named as conotoxins or conopeptides. These conotoxins have proven to be valuable pharmacological probes and potential drugs due to their high specificity and affinity to ion channels, receptors, and transporters in the nervous systems of target prey and humans. Several research groups, including ours, have examined the venom gland of cone snails using a combination of transcriptomic and proteomic sequencing, and revealed the existence of hundreds of conotoxin transcripts and thousands of conopeptides in each Conus species. Over 2000 nucleotide and 8000 peptide sequences of conotoxins have been published, and the number is still increasing quickly. However, more than 98% of these sequences still lack 3D structural and functional information. With the rapid development of genomics and bioinformatics in recent years, functional predictions and investigations on conotoxins are making great progress in promoting the discovery of novel drugs. For example, ω-MVIIA was approved by the U.S. Food and Drug Administration in 2004 to treat chronic pain, and nine more conotoxins are at various stages of preclinical or clinical evaluation. In short, the genus Conus, the big family of cone snails, has become an important genetic resource for conotoxin identification and drug development.
- Published
- 2017
11. Proteomic Analysis of the Predatory Venom of Conus striatus Reveals Novel and Population-Specific κA-Conotoxin SIVC.
- Author
-
Saintmont F, Cazals G, Bich C, and Dutertre S
- Subjects
- Animals, Venoms metabolism, Proteomics, Tandem Mass Spectrometry, Conus Snail chemistry, Conotoxins chemistry
- Abstract
Animal venoms are a rich source of pharmacological compounds with ecological and evolutionary significance, as well as with therapeutic and biotechnological potentials. Among the most promising venomous animals, cone snails produce potent neurotoxic venom to facilitate prey capture and defend against aggressors. Conus striatus , one of the largest piscivorous species, is widely distributed, from east African coasts to remote Polynesian Islands. In this study, we investigated potential intraspecific differences in venom composition between distinct geographical populations from Mayotte Island (Indian Ocean) and Australia (Pacific Ocean). Significant variations were noted among the most abundant components, namely the κA-conotoxins, which contain three disulfide bridges and complex glycosylations. The amino acid sequence of a novel κA-conotoxin SIVC, including its N-terminal acetylated variant, was deciphered using tandem mass spectrometry (MS/MS). In addition, the glycosylation pattern was found to be consisting of two HexNAc and four Hex for the Mayotte population, which diverge from the previously characterized two HexNAc and three Hex combinations for this species, collected elsewhere. Whereas the biological and ecological roles of these modifications remain to be investigated, population-specific glycosylation patterns provide, for the first time, a new level of intraspecific variations in cone snail venoms.
- Published
- 2022
- Full Text
- View/download PDF
12. Venomics Reveals a Non-Compartmentalised Venom Gland in the Early Diverged Vermivorous Conus distans .
- Author
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Prashanth JR, Dutertre S, Rai SK, and Lewis RJ
- Subjects
- Animals, Mollusk Venoms chemistry, Peptides, Transcriptome, Venoms, Conotoxins chemistry, Conotoxins genetics, Conus Snail genetics
- Abstract
The defensive use of cone snail venom is hypothesised to have first arisen in ancestral worm-hunting snails and later repurposed in a compartmentalised venom duct to facilitate the dietary shift to molluscivory and piscivory. Consistent with its placement in a basal lineage, we demonstrate that the C. distans venom gland lacked distinct compartmentalisation. Transcriptomics revealed C. distans expressed a wide range of structural classes, with inhibitory cysteine knot (ICK)-containing peptides dominating. To better understand the evolution of the venom gland compartmentalisation, we compared C. distans to C. planorbis , the earliest diverging species from which a defence-evoked venom has been obtained, and fish-hunting C. geographus from the Gastridium subgenus that injects distinct defensive and predatory venoms. These comparisons support the hypothesis that venom gland compartmentalisation arose in worm-hunting species and enabled repurposing of venom peptides to facilitate the dietary shift from vermivory to molluscivory and piscivory in more recently diverged cone snail lineages.
- Published
- 2022
- Full Text
- View/download PDF
13. A New Member of Gamma-Conotoxin Family Isolated from Conus princeps Displays a Novel Molecular Target.
- Author
-
Bernáldez J, Jiménez S, González LJ, Ferro JN, Soto E, Salceda E, Chávez D, Aguilar MB, and Licea-Navarro A
- Subjects
- Amino Acid Sequence, Animals, Conotoxins chemistry, Conotoxins isolation & purification, Female, Ganglia, Spinal cytology, Ganglia, Spinal physiology, Male, Molecular Sequence Data, Neurons physiology, Peptides chemistry, Peptides isolation & purification, Rats, Long-Evans, Calcium Channels physiology, Conotoxins pharmacology, Conus Snail, Neurons drug effects, Peptides pharmacology
- Abstract
A novel conotoxin, named as PiVIIA, was isolated from the venom of Conus princeps, a marine predatory cone snail collected in the Pacific Southern Coast of Mexico. Chymotryptic digest of the S-alkylated peptide in combination with liquid chromatography coupled to tandem mass spectrometry, were used to define the sequencing of this peptide. Eleven N-terminal amino acids were verified by automated Edman degradation. PiVIIA is a 25-mer peptide (CDAOTHYCTNYWγCCSGYCγHSHCW) with six cysteine residues forming three disulphide bonds, a hydroxyproline (O) and two gamma carboxyglutamic acid (γ) residues. Based on the arrangement of six Cys residues (C-C-CC-C-C), this conotoxin might belong to the O2-superfamily. Moreover, PiVIIA has a conserved motif (-γCCS-) that characterizes γ-conotoxins from molluscivorous Conus. Peptide PiVIIA has 45% sequence identity with γ-PnVIIA-the prototype of this family. Biological activity of PiVIIA was assessed by voltage-clamp recording in rat dorsal root ganglion neurons. Perfusion of PiVIIA in the µM range produces a significant increase in the Ca(2+) currents, without significantly modifying the Na⁺, K⁺ or proton-gated acid sensing ionic currents. These results indicate that PiVIIA is a new conotoxin whose activity deserves further studies to define its potential use as a positive modulator of neuronal activity.
- Published
- 2016
- Full Text
- View/download PDF
14. Venomics Reveals a Non-Compartmentalised Venom Gland in the Early Diverged Vermivorous
- Author
-
Jutty Rajan, Prashanth, Sebastien, Dutertre, Subash Kumar, Rai, and Richard J, Lewis
- Subjects
Venoms ,Conus Snail ,Animals ,Mollusk Venoms ,Conotoxins ,Peptides ,Transcriptome - Abstract
The defensive use of cone snail venom is hypothesised to have first arisen in ancestral worm-hunting snails and later repurposed in a compartmentalised venom duct to facilitate the dietary shift to molluscivory and piscivory. Consistent with its placement in a basal lineage, we demonstrate that the
- Published
- 2022
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