Isolation and characterisation of five neurotoxic and cardiotoxic polypeptides from the sea anemone Anthopleura elegantissima

Bruhn, Thomas; Schaller, C. W.; Schulze, Christian; Sánchez‐Rodríguez, Judith; Dannmeier, C; Ravens, Ursula; Heubach, Jürgen F.; Eckhardt, Kai‐Uwe; Schmidtmayer, Johann; Schmidt, H.; Aneiros, Abel; Wächter, Elmar; Béress, L.

doi:10.1016/s0041-0101(00)00199-9

Cited by 63 publications

(37 citation statements)

References 29 publications

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“…It produces several Type I neurotoxins with remarkable homology to Av2 (up to 96% identity and 98% similarity) [36]. We macerated A. elegantissima tentacles and stained them with the anti-Nv1 serum.…”

Section: Resultsmentioning

confidence: 99%

Neurotoxin localization to ectodermal gland cells uncovers an alternative mechanism of venom delivery in sea anemones

et al. 2011

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Jellyfish, hydras, corals and sea anemones (phylum Cnidaria) are known for their venomous stinging cells, nematocytes, used for prey and defence. Here we show, however, that the potent Type I neurotoxin of the sea anemone Nematostella vectensis, Nv1, is confined to ectodermal gland cells rather than nematocytes. We demonstrate massive Nv1 secretion upon encounter with a crustacean prey. Concomitant discharge of nematocysts probably pierces the prey, expediting toxin penetration. Toxin efficiency in sea water is further demonstrated by the rapid paralysis of fish or crustacean larvae upon application of recombinant Nv1 into their medium. Analysis of other anemone species reveals that in Anthopleura elegantissima, Type I neurotoxins also appear in gland cells, whereas in the common species Anemonia viridis, Type I toxins are localized to both nematocytes and ectodermal gland cells. The nematocyte-based and gland cell-based envenomation mechanisms may reflect substantial differences in the ecology and feeding habits of sea anemone species. Overall, the immunolocalization of neurotoxins to gland cells changes the common view in the literature that sea anemone neurotoxins are produced and delivered only by stinging nematocytes, and raises the possibility that this toxin-secretion mechanism is an ancestral evolutionary state of the venom delivery machinery in sea anemones.

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Section: Resultsmentioning

confidence: 99%

Neurotoxin localization to ectodermal gland cells uncovers an alternative mechanism of venom delivery in sea anemones

et al. 2011

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“…The toxin APEKTx1 was purified as described previously [16,17,19]. The fraction containing APEKTx1 was further purificated by RP-HPLC with a semi preparative Vydac C18 column (4.6X250 mm).…”

Section: Toxin Purificationmentioning

confidence: 99%

“…Based on structural differences and activity profile, these potassium channel toxins can be divided into 4 structural classes [11,[13][14][15]. Up to date 6 toxins from A. elegantissima have been isolated and characterized: APE1-1, APE1-2, APE2-2 and ApC which are type 1 sodium channel toxins; APETx1 a selective modifier of the human ether a go-go related gene K + channel (hERG) and APETx2 which specifically inhibits the Acid Sensing Ion Channel (ASIC3) [15][16][17][18]. In this work we present the purification, biochemical analysis and electrophysiological characterization of a very potent and selective K V 1.1 blocker which represents the newest member of the sea anemone type 2 potassium channel toxins.…”

Section: Introductionmentioning

confidence: 99%

A bifunctional sea anemone peptide with Kunitz type protease and potassium channel inhibiting properties

Peigneur¹,

Billen²,

Derua³

et al. 2011

Biochemical Pharmacology

103

101

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This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. Page 1 of 22A c c e p t e d M a n u s c r i p t Abstract Sea anemone venom is a known source of interesting bioactive compounds, including peptide toxins which are invaluable tools for studying structure and function of voltage-gated potassium channels. APEKTx1 is a novel peptide isolated from the sea anemone Anthopleura elegantissima, containing 63 amino acids cross-linked by 3 disulfide bridges. Sequence alignment reveals that APEKTx1 is a new member of the type 2 sea anemone peptides targeting voltage-gated potassium channels (K V 's), which also include the kalicludines from Anemonia sulcata. Similar to the kalicludines, APEKTx1 shares structural homology with both the basic pancreatic trypsin inhibitor (BPTI), a very potent Kunitz-type protease inhibitor, and dendrotoxins which are powerful blockers of voltage-gated potassium channels. In this study, APEKTx1 has been subjected to a screening on a wide range of 23 ion channels expressed in Xenopus leavis oocytes: 13 cloned voltage-gated potassium channels (K V 1.1-K V 1.6, K V 1.1 triple mutant, K V 2.1, K V 3.1, K V 4.2, K V 4.3, hERG, the insect channel Shaker IR), 2 cloned hyperpolarization-activated cyclic nucleotidesensitive cation non-selective channels (HCN1 and HCN2) and 8 cloned voltage-gated sodium channels (Na V 1.2-Na V 1.8 and the insect channel DmNa V 1). Our data shows that APEKTx1 selectively blocks K V 1.1 channels in a very potent manner with an IC 50 value of 0.9 nM. Furthermore, we compared the trypsin inhibitory activity of this toxin with BPTI. APEKTx1 inhibits trypsin with a dissociation constant of 124 nM. In conclusion, this study demonstrates that APEKTx1 has the unique feature to combine the dual functionality of a potent and selective blocker of K V 1.1 channels with that of a competitive inhibitor of trypsin.Keywords Anthopleura elegantissima · K V channel inhibitor · sea anemone toxin · protease inhibitor ·

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“…The corresponding three-dimensional representation in Figure 4 results in The sequences were obtained from the following papers: AeI (Actinia equina): [27], AETX I (Anemonia erythraea): [28], APE 1-1, APE 1-2, APE 2-1 (Anthopleura elegantissima): [29], AFT-I, AFT-II (Anthopleura fuscoviridis): [30], ATX-Ia, ATX-I, ATX-II, ATX-V ATX-III, ATX-IV (Anemonia sulcata): [31][32][33][34][35][36], Ap-A, Ap-B, PCR1-2, PCR 2-1, PCR2-5, PCR 2-10, PCR 3-3, PCR 3-6, PCR 3-7 (Anthopleura xanthogrammica): [37][38][39], BcIII (Bunodosoma caissarum): [40], Bg II, Bg III (Bunodosoma granulifera): [41], Cp II (Condylactis passiflora): [42], RTX-I, RTX-II, RTX-III, RTX-IV, RTX-V (Radianthus macrodactylus/previously Heteractis macrodactylus): [43][44][45], RpII, RpIII (Radianthus paumotensis/previously Heteractis magnífica or Heteractis paumotensis): [46][47], Sh I (Stichodactylae helianthus): [48], CLX-I, CLX-II (Calliactis parasitica): [19], Halcurin (Halcurias carlgreni): [49], PA-TX (Parasicyonis actinostoloides/previously Entacmaea quadricolor): [50].…”

Section: Resultsmentioning

confidence: 99%

Functional discrimination of sea anemone neurotoxins using 3D-plotting

et al. 2009

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Abstract:One of the most important goals in structural biology is the identification of functional relationships among the structure of proteins and peptides. The purpose of this study was to (1) generate a model based on theoretical and computational considerations among amino acid sequences within select neurotoxin peptides, and (2) compare the relationship these values have to the various toxins tested. We employed isolated neurotoxins from sea anemones with established specific potential to act on voltage-dependent sodium and potassium channel activity as our model. Values were assigned to each amino acid in the peptide sequence of the neurotoxins tested using the Number of Lareo and Acevedo algorithm (NULA). Once the NULA number was obtained, it was then plotted using three dimensional space coordinates. The results of this study allow us to report, for the first time, that there is a different numerical and functional relationship between the sequences of amino acids from sea anemone neurotoxins, and the resulting numerical relationship for each peptide, or NULA number, has a unique location in three-dimensional space.

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Isolation and characterisation of five neurotoxic and cardiotoxic polypeptides from the sea anemone Anthopleura elegantissima

Cited by 63 publications

References 29 publications

Neurotoxin localization to ectodermal gland cells uncovers an alternative mechanism of venom delivery in sea anemones

Neurotoxin localization to ectodermal gland cells uncovers an alternative mechanism of venom delivery in sea anemones

A bifunctional sea anemone peptide with Kunitz type protease and potassium channel inhibiting properties

Functional discrimination of sea anemone neurotoxins using 3D-plotting

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