Structural and functional characterisation of a novel peptide from the Australian sea anemone Actinia tenebrosa
Elnahriry, K.A.; Wai, D.C.C.; Krishnarjuna, B.; Badawy, N.N.; Chittoor, B.; MacRaild, C.A.; Williams-Noonan, B.J.; Surm, J.M.; Chalmers, D.K.; Zhang, A.H.; Peigneur, S.; Mobli, M.; Tytgat, J.; Prentis, P.; Norton, R.S. (2019). Structural and functional characterisation of a novel peptide from the Australian sea anemone Actinia tenebrosa. Toxicon 168: 104-112. https://dx.doi.org/10.1016/j.toxicon.2019.07.002
In: Toxicon. Elsevier: Oxford. ISSN 0041-0101; e-ISSN 1879-3150, meer
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| Trefwoorden |
Actinia tenebrosa Farquhar, 1898 [WoRMS]
Marien/Kust |
| Author keywords |
Sea anemone; Cysteine-containing peptide; Structure; NMR spectroscopy;Lipid interactions |
| Auteurs | | Top |
- Elnahriry, K.A.
- Wai, D.C.C.
- Krishnarjuna, B.
- Badawy, N.N.
- Chittoor, B.
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- MacRaild, C.A.
- Williams-Noonan, B.J.
- Surm, J.M.
- Chalmers, D.K.
- Zhang, A.H.
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- Peigneur, S., meer
- Mobli, M.
- Tytgat, J., meer
- Prentis, P.
- Norton, R.S.
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| Abstract |
Sea anemone venoms have long been recognised as a rich source of peptides with interesting pharmacological and structural properties. Our recent transcriptomic studies of the Australian sea anemone Actinia tenebrosa have identified a novel 13-residue peptide, U-AITx-Ate1. U-AITx-Ate1 contains a single disulfide bridge and bears no significant homology to previously reported amino acid sequences of peptides from sea anemones or other species. We have produced U-AITx-Ate1 using solid-phase peptide synthesis, followed by oxidative folding and purification of the folded peptide using reversed-phase high-performance liquid chromatography. The solution structure of U-AITx-Ate1 was determined based on two-dimensional nuclear magnetic resonance spectroscopic data. Diffusion-ordered NMR spectroscopy revealed that U-AITx-Ate1 was monomeric in solution. Perturbations in the 1D 1H NMR spectrum of U-AITx-Ate1 in the presence of dodecylphosphocholine micelles together with molecular dynamics simulations indicated an interaction of U-AITx-Ate1 with lipid membranes, although no binding was detected to 100% POPC and 80% POPC: 20% POPG lipid nanodiscs by isothermal titration calorimetry. Functional assays were performed to explore the biological activity profile of U-AITx-Ate1. U-AITx-Ate1 showed no activity in voltage-clamp electrophysiology assays and no change in behaviour and mortality rates in crustacea. Moderate cytotoxic activity was observed against two breast cancer cell lines. |
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