Skip to main content
Log in

New Sea Anemone Toxin RTX-VI Selectively Modulates Voltage-Gated Sodium Channels

  • BIOCHEMISTRY, BIOPHYSICS, AND MOLECULAR BIOLOGY
  • Published:
Doklady Biochemistry and Biophysics Aims and scope Submit manuscript

Abstract

A new neurotoxin RTX-VI that modulates the voltage-gated sodium channels (NaV) was isolated from the ethanolic extract of the sea anemone Heteractis crispa. Its amino acid sequence was determined using the combination of Edman degradation and tandem mass spectrometry. RTX-VI turned out to be an unusual natural analogue of the previously described sea anemone toxin RTX-III. The RTX-VI molecule consists of two disulfide-linked peptide chains and is devoid of Arg13, which is important for the selectivity and affinity of such peptides for the NaV channels. Electrophysiological screening of RTV-VI on NaV channel subtypes showed its selective interaction with the central nervous system (NaV1.2, NaV1.6) and insect (BgNaV1, VdNaV1) sodium channels.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1.
Fig. 2.
Fig. 3.

Similar content being viewed by others

REFERENCES

  1. Deuis, J., Mueller, A., Israel, M., et al., The pharmacology of voltage-gated sodium channel activators, Neuropharmacology, 2017, vol. 127, pp. 87–108. https://doi.org/10.1016/j.neuropharm.2017.04.0

    Article  CAS  PubMed  Google Scholar 

  2. Sintsova, O., Gladkikh, I., Chausova, V., et al., Peptide fingerprinting of the sea anemone Heteractis magnifica mucus revealed neurotoxins, Kunitz-type proteinase inhibitors and a β-defensin α-amylase inhibitor, J. Proteomics, 2017, vol. 173, pp. 12–21. https://doi.org/10.1016/j.jprot.2017.11.019

    Article  CAS  PubMed  Google Scholar 

  3. Frazão, B., Vasconcelos, V., and Antunes, A., Sea anemone (Cnidaria, Anthozoa, Actiniaria) toxins: an overview, Mar. Drugs, 2012, vol. 10, no. 12, pp. 1812–1851. https://doi.org/10.3390/md10081812

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Kalina, R., Gladkikh, I., Dmitrenok, P., et al., New APETx-like peptides from sea anemone Heteractis crispa modulate ASIC1a channels, Peptides, 2018, vol. 104, pp. 41–49. https://doi.org/10.1016/j.peptides.2018.04.013

    Article  CAS  PubMed  Google Scholar 

  5. Rauer, H., Pennington, M., Cahalan, M., et al., Structural conservation of the pores of calcium-activated and voltage-gated potassium channels determined by a sea anemone toxin, J. Biol. Chem., 1999, vol. 274, no. 31, pp. 21885–21892. https://doi.org/10.1074/jbc.274.31.21885

    Article  CAS  PubMed  Google Scholar 

  6. Monastyrnaya, M., Peigneur, S., Zelepuga, E., et al., Kunitz-type peptide HCRG21 from the sea anemone Heteractis crispa is a full antagonist of the TRPV1 receptor, Mar. Drugs, 2016, vol. 14, no. 12, p. 229. https://doi.org/10.3390/md14120229

    Article  CAS  PubMed Central  Google Scholar 

  7. Logashina, Y.A., Mosharova, I.V., Korolkova, Y.V., et al., Peptide from sea anemone Metridium senile affects transient receptor potential ankyrin-repeat 1 (TRPA1) function and produces analgesic effect, J. Biol. Chem., 2017, vol. 292, no. 7, pp. 2992–3004. https://doi.org/10.1074/jbc.M116.757369

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Schweitz, H., Bidard, J., Frelin, C., et al., Purification, sequence, and pharmacological properties of sea anemone toxins from Radianthus paumotensis. A new class of sea anemone toxins acting on the sodium channel, Biochemistry, 1985, vol. 24, no. 14, pp. 3554–3561. https://doi.org/10.1021/bi00335a025

    Article  CAS  PubMed  Google Scholar 

  9. Salgado, V.L. and Kem, W.R., Actions of three structurally distinct sea anemone toxins on crustacean and insect sodium channels, Toxicon, 1992, vol. 30, no. 11, pp. 1365–1381. https://doi.org/10.1016/0041-0101(92)90512-4

    Article  CAS  PubMed  Google Scholar 

  10. Honma, T., Kawahata, S., Ishida, M., et al., Novel peptide toxins from the sea anemone Stichodactyla haddoni, Peptides, 2008, vol. 29, no. 4, pp. 536–544. https://doi.org/10.1016/j.peptides.2007.12.010

    Article  CAS  PubMed  Google Scholar 

  11. Zykova, T.A., Vinokurov, L.M., Kozlovskaya, E.P., et al., Amino acid sequence of neurotoxin III from the sea anemone Radianthus macrodactylus, Bioorg. Khim., 1985, vol. 11, no. 3, pp. 302–310.

    CAS  Google Scholar 

  12. Wilcox, G.R., Fogh, R.H., and Norton, R.S., Refined structure in solution of the sea anemone neurotoxin ShI, J. Biol. Chem., 1993, vol. 268, no. 33, pp. 24707–24719.

    CAS  PubMed  Google Scholar 

  13. Pallaghy, P.K., Scanlon, M., Monks, S., et al., Three-dimensional structure in solution of the polypeptide cardiac stimulant anthopleurin-A, Biochemistry, 1995, vol. 34, no. 11, pp. 3782–3794. https://doi.org/10.1021/bi00011a036

    Article  CAS  PubMed  Google Scholar 

  14. Wullschleger, B., Kuhn-Nentwig, L., Tromp, J., et al., CSTX-13, a highly synergistically acting two-chain neurotoxic enhancer in the venom of the spider Cupiennius salei (Ctenidae), Proc. Natl. Acad. Sci. U. S. A., 2004, vol. 101, no. 31, pp. 11251–11256. https://doi.org/10.1073/pnas.0402226101

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

ACKNOWLEDGMENTS

The study was carried out on the equipment of the Collective Facilities Center “The Far Eastern Center for Structural Molecular Research (NMR/MS) PIBOC FEB RAS.”

Funding

This work was supported by the Russian Foundation for Basic Research (grant no. 18-04-00631).

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to R. S. Kalina.

Ethics declarations

Conflict of interest. The authors declare that the studies were conducted in the absence of any commercial or financial relationship that could be construed as a potential conflict of interest.

Statement on the welfare of animals. All applicable international, national, and/or institutional guidelines for the care and use of animals were followed.

Additional information

Translated by M. Batrukova

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Kalina, R.S., Peigneur, S., Gladkikh, I.N. et al. New Sea Anemone Toxin RTX-VI Selectively Modulates Voltage-Gated Sodium Channels. Dokl Biochem Biophys 495, 292–295 (2020). https://doi.org/10.1134/S1607672920060071

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1134/S1607672920060071

Keywords:

Navigation