Phyla Molluska: The Venom Apparatus of Cone Snails

Dutertre, Sébastien; Griffin, John; Lewis, Richard J.

doi:10.1007/978-94-007-6650-1_8-1

Cited by 5 publications

(4 citation statements)

References 25 publications

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“…Cone snails provide one of the highest venom diversities among venomous animals, with current estimates of 1 million different bioactive conotoxins to exist . Less than 1% of these have been sequenced (∼10,000), and only a small fraction of these have been characterized pharmacologically.…”

Section: Conotoxin Classification and Nomenclaturementioning

confidence: 99%

Conotoxins: Chemistry and Biology

et al. 2019

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The venom of the marine predatory cone snails (genus Conus) has evolved for prey capture and defense, providing the basis for survival and rapid diversification of the now estimated 750+ species. A typical Conus venom contains hundreds to thousands of bioactive peptides known as conotoxins. These mostly disulfide-rich and well-structured peptides act on a wide range of targets such as ion channels, G protein-coupled receptors, transporters, and enzymes. Conotoxins are of interest to neuroscientists as well as drug developers due to their exquisite potency and selectivity, not just against prey but also mammalian targets, thereby providing a rich source of molecular probes and therapeutic leads. The rise of integrated venomics has accelerated conotoxin discovery with now well over 10,000 conotoxin sequences published. However, their structural and pharmacological characterization lags considerably behind. In this review, we highlight the diversity of new conotoxins uncovered since 2014, their three-dimensional structures and folds, novel chemical approaches to their syntheses, and their value as pharmacological tools to unravel complex biology. Additionally, we discuss challenges and future directions for the field.

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Section: Conotoxin Classification and Nomenclaturementioning

confidence: 99%

Conotoxins: Chemistry and Biology

et al. 2019

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“…The marine cone snails of the genus Conus comprise a family of approximately 700 species that produce venom made of a complex toxin repertoire to capture prey and defend against predators. , The best characterized components in their venom are the disulfide rich peptides termed conotoxins . The conotoxins have attracted the attention of researchers because of their high affinity and selectivity for a range of ion channels, receptors, and transporters in the neuromuscular system.…”

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confidence: 99%

MrIC, a Novel α-Conotoxin Agonist in the Presence of PNU at Endogenous α7 Nicotinic Acetylcholine Receptors

et al. 2013

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α-Conotoxins are competitive antagonists of nicotinic acetylcholine receptors (nAChRs). Their high selectivity and affinity for the various subtypes of nAChRs have led to significant advances in our understanding of the structure and function of these key ion channels. Here we report the discovery of a novel 4/7 α-conotoxin, MrIC from the venom duct of Conus marmoreus, which acts as an agonist at the endogenous human α7 nAChR in SH-SY5Y cells pretreated with PNU120596 (PNU). This unique agonist activity of MrIC at α7 nAChRs may guide the development of novel α7 nAChR modulators.

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“…Conopeptides are peptides that have been evolved by marine cone snails to protect against predators and to capture prey. Each species of cone snail may produce over 1,000 different peptides [1] and estimates for the total number of conopeptides range from 50,000 to millions, [2,3] but structural characterization remains sparse. The targets for these conopeptides are varied and include several protein classes of significance in human disease such as ion channels and G protein-coupled receptors (GPCRs).…”

Section: Introductionmentioning

confidence: 99%

Delta-Conotoxin Structure Prediction and Analysis through Large-scale Comparative and Deep Learning Modeling Approaches

Gonen,

McCarthy

2024

Preprint

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The delta-conotoxins, a class of peptide produced in the venom of cone snails, are of interest due to their ability to inhibit the inactivation of voltage-gated sodium channels causing paralysis and other neurological responses, but difficulties in their isolation and synthesis have made structural characterization challenging. Taking advantage of recent breakthroughs in computational algorithms for structure prediction that have made modeling especially useful when experimental data is sparse, this work uses both the deep-learning based algorithm AlphaFold and comparative modeling method RosettaCM to model and analyze 18 previously uncharacterized delta-conotoxins derived from piscivorous, vermivorous, and molluscivorous cone snails. The models provide useful insights into structural aspects of these peptides and suggest features likely to be significant in influencing their binding and different pharmacological activities against their targets, with implications for drug development. Additionally, the described protocol provides a roadmap for the modeling of similar disulfide-rich peptides by these complementary methods.

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Phyla Molluska: The Venom Apparatus of Cone Snails

Cited by 5 publications

References 25 publications

Conotoxins: Chemistry and Biology

Conotoxins: Chemistry and Biology

MrIC, a Novel α-Conotoxin Agonist in the Presence of PNU at Endogenous α7 Nicotinic Acetylcholine Receptors

Delta-Conotoxin Structure Prediction and Analysis through Large-scale Comparative and Deep Learning Modeling Approaches

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