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Identification, chemical synthesis, structure, and function of a new KV1 channel blocking peptide from Oulactis sp.
Sunanda, P.; Krishnarjuna, B.; Peigneur, S.; Mitchell, M.L.; Estrada, R.; Villegas-Moreno, J.; Pennington, M.W.; Tytgat, J.; Norton, R.S. (2018). Identification, chemical synthesis, structure, and function of a new KV1 channel blocking peptide from Oulactis sp. Peptide Science 110(4): e24073. https://dx.doi.org/10.1002/pep2.24073
In: Peptide Science. John Wiley & Sons: Hoboken. e-ISSN 2475-8817
Peer reviewed article  
Beschikbaar in  Auteurs 
Trefwoorden
    Oulactis Milne Edwards & Haime, 1851 [WoRMS]
    Marien/Kust
Author keywords
    cysteine-rich peptide; isomers; K-V channel; NMR spectroscopy; OspTx2a;sea anemone; structure
Auteurs  Top 
  • Sunanda, P.
  • Krishnarjuna, B.
  • Peigneur, S.
  • Mitchell, M.L.
  • Estrada, R.
  • Villegas-Moreno, J.
  • Pennington, M.W.
  • Tytgat, J., meer
  • Norton, R.S.
Abstract
    Rapid progress in transcriptomic and proteomic studies of sea anemones has led to the identification of a large number of new peptide sequences. Some of these peptides have high sequence similarity and identical cysteine frameworks to those of previously reported sequences. One such peptide we have identified from a transcriptomic study of Oulactis sp is OspTx2a, which has a cysteine framework similar to that of ShK (from Stichodactyla helianthus) and BgK (from Bunodosoma granulifera). This peptide was made using solid‐phase peptide synthesis, but, upon oxidative folding, it generated two peptides with identical masses (OspTx2a‐p1 and OspTx2a‐p2) that were distinguishable by high‐performance liquid chromatography. The structures of OspTx2a‐p1 and OspTx2a‐p2 were determined using nuclear magnetic resonance spectroscopy, and voltage‐clamp electrophysiology assays were performed in order to assess the activity against a range of potassium channels. The structures of the two peptides were very similar to each other and to BgK, with the same disulfide bond connectivities, and both had an all‐trans backbone conformation. In functional assays, both OspTx2a‐p1 and OspTx2a‐p2 inhibited KV1.2 and KV1.6 channel currents at low µM concentrations, with similar but not identical IC50 values. Peptides containing a C‐terminal Cys residue are particularly sensitive to racemization at this residue, and the two products obtained for OspTx2a could be a consequence of racemization of the Cys residue at its C‐terminus during synthesis. NMR chemical shift differences between the two products and their structural preferences for a d‐Cys residue were consistent with this interpretation.
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