Synthesis, folding, structure and activity of a predicted peptide from the sea anemone Oulactis sp. with an ShKT fold

Bankala Krishnarjuna, Jessica Villegas-Moreno, Michela L. Mitchell, Agota Csoti, Steve Peigneur, Carlos Amero, Michael W. Pennington, Jan Tytgat, Gyorgy Panyi, Raymond S. Norton

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Abstract

Sea anemone venom is rich in bioactive compounds, including peptides containing multiple disulfide bridges. In a transcriptomic study on Oulactis sp., we identified the putative 36-residue peptide, OspTx2b, which is an isoform of the KV channel blocker OspTx2a (Sunanda P et al. [2018] Identification, chemical synthesis, structure and function of a new KV1 channel blocking peptide from Oulactis sp. Peptide Science, in press). As OspTx2b contains a ShK/BgK-like cysteine framework, with high amino acid sequence similarity to BgK, we were interested to investigate its structure and function. The solution structure of OspTx2b was determined using nuclear magnetic resonance spectroscopy. OspTx2b does indeed possess a BgK-like scaffold, with the same disulfide bond connectivities. The orientation of the Lys-Tyr dyad in OspTx2b is more similar to that in ShK than in BgK. However, it failed to show against a range of voltage-gated potassium channels in Xenopus oocytes and human T lymphocytes. OspTx2b also showed no growth inhibitory activity against several strains of bacteria and fungi. Having a BgK-like fold with the Lys-Tyr dyad but no BgK-like activity highlights the importance of key amino acid residues in BgK that are missing in OspTx2b. The lack of activity against the KV channels assessed in this study emphasises that the ShK/BgK scaffold is capable of supporting functional activity beyond potassium channel blockade.

Original languageEnglish
Pages (from-to)50-59
Number of pages10
JournalToxicon
Volume150
DOIs
Publication statusPublished - 1 Aug 2018

Keywords

  • Cysteine-rich peptide
  • NMR spectroscopy
  • OspTx2b
  • Potassium channel
  • Sea anemone
  • Structure

Cite this

Krishnarjuna, B., Villegas-Moreno, J., Mitchell, M. L., Csoti, A., Peigneur, S., Amero, C., Pennington, M. W., Tytgat, J., Panyi, G., & Norton, R. S. (2018). Synthesis, folding, structure and activity of a predicted peptide from the sea anemone Oulactis sp. with an ShKT fold. Toxicon, 150, 50-59. https://doi.org/10.1016/j.toxicon.2018.05.006