Sea Anemone Toxins: A Structural Overview

Madio, Bruno; King, Glenn F.; Undheim, Eivind A. B.

doi:10.3390/md17060325

Cited by 63 publications

(98 citation statements)

References 155 publications

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“…The type I and II toxins are one of the most-studied groups of sea anemone peptides as they constitute a majority of the venom components [9,41]. Despite this fact, few toxins have been studied in terms of their ability to distinguish closely related Na V subtypes.…”

Section: Discussionmentioning

confidence: 99%

New Insights into the Type II Toxins from the Sea Anemone Heteractis crispa

Kalina

Peigneur

Zelepuga

et al. 2020

Toxins

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Toxins modulating NaV channels are the most abundant and studied peptide components of sea anemone venom. Three type-II toxins, δ-SHTX-Hcr1f (= RpII), RTX-III, and RTX-VI, were isolated from the sea anemone Heteractis crispa. RTX-VI has been found to be an unusual analog of RTX-III. The electrophysiological effects of Heteractis toxins on nine NaV subtypes were investigated for the first time. Heteractis toxins mainly affect the inactivation of the mammalian NaV channels expressed in the central nervous system (NaV1.1–NaV1.3, NaV1.6) as well as insect and arachnid channels (BgNaV1, VdNaV1). The absence of Arg13 in the RTX-VI structure does not prevent toxin binding with the channel but it has changed its pharmacological profile and potency. According to computer modeling data, the δ-SHTX-Hcr1f binds within the extracellular region of the rNaV1.2 voltage-sensing domain IV and pore-forming domain I through a network of strong interactions, and an additional fixation of the toxin at the channel binding site is carried out through the phospholipid environment. Our data suggest that Heteractis toxins could be used as molecular tools for NaV channel studies or insecticides rather than as pharmacological agents.

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Section: Discussionmentioning

confidence: 99%

New Insights into the Type II Toxins from the Sea Anemone Heteractis crispa

Kalina

Peigneur

Zelepuga

et al. 2020

Toxins

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“…Due to the large diversity of toxins produced from sea anemones and both their functional convergence and promiscuity, classification of sea anemone toxins has proven difficult. A recent review has attempted to circumvent this by classifying sea anemone proteinaceous toxins into three major groups: (1) enzymes, (2) nonenzymatic cytotoxins, or (3) nonenzymatic peptide neurotoxins [103]. The Kv channel targeting sea anemone toxins all fall into the third group, peptide neurotoxins, which can be further classified into 9 structural families.…”

Section: Cnidarian Peptides That Inhibit Kv1 Channelsmentioning

confidence: 99%

Marine Toxins Targeting Kv1 Channels: Pharmacological Tools and Therapeutic Scaffolds

et al. 2020

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Toxins from marine animals provide molecular tools for the study of many ion channels, including mammalian voltage-gated potassium channels of the Kv1 family. Selectivity profiling and molecular investigation of these toxins have contributed to the development of novel drug leads with therapeutic potential for the treatment of ion channel-related diseases or channelopathies. Here, we review specific peptide and small-molecule marine toxins modulating Kv1 channels and thus cover recent findings of bioactives found in the venoms of marine Gastropod (cone snails), Cnidarian (sea anemones), and small compounds from cyanobacteria. Furthermore, we discuss pivotal advancements at exploiting the interaction of κM-conotoxin RIIIJ and heteromeric Kv1.1/1.2 channels as prevalent neuronal Kv complex. RIIIJ’s exquisite Kv1 subtype selectivity underpins a novel and facile functional classification of large-diameter dorsal root ganglion neurons. The vast potential of marine toxins warrants further collaborative efforts and high-throughput approaches aimed at the discovery and profiling of Kv1-targeted bioactives, which will greatly accelerate the development of a thorough molecular toolbox and much-needed therapeutics.

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“…One of the most representative Kv1.3 blockers is sea anemone toxin peptides. Sea anemones have a rich source of peptide toxins acting on ion channels, which are presumably present in special spiny organelles (nematodes) (Madio et al, 2019). These toxins can be used to catch prey as well as defend against predators (Prentis et al, 2018).…”

Section: Introductionmentioning

confidence: 99%