PhcrTx2, a New Crab-Paralyzing Peptide Toxin from the Sea Anemone Phymanthus crucifer

• Main Authors: Armando Alexei Rodríguez, Anoland Garateix, Emilio Salceda, Steve Peigneur, André Junqueira Zaharenko, Tirso Pons, Yúlica Santos, Roberto Arreguín, Ludger Ständker, Wolf-Georg Forssmann, Jan Tytgat, Rosario Vega, Enrique Soto
• Format: Article
• Language: English
• Published: MDPI AG 2018-02-01
• Series: Toxins
• Subjects: sea anemone; neutoxin; glutamate receptor; defensin-like fold; ion channels; Phymanthus crucifer
• Online Access: http://www.mdpi.com/2072-6651/10/2/72

Sea anemones produce proteinaceous toxins for predation and defense, including peptide toxins that act on a large variety of ion channels of pharmacological and biomedical interest. Phymanthus crucifer is commonly found in the Caribbean Sea; however, the chemical structure and biological activity of its toxins remain unknown, with the exception of PhcrTx1, an acid-sensing ion channel (ASIC) inhibitor. Therefore, in the present work, we focused on the isolation and characterization of new P. crucifer toxins by chromatographic fractionation, followed by a toxicity screening on crabs, an evaluation of ion channels, and sequence analysis. Five groups of toxic chromatographic fractions were found, and a new paralyzing toxin was purified and named PhcrTx2. The toxin inhibited glutamate-gated currents in snail neurons (maximum inhibition of 35%, IC50 4.7 µM), and displayed little or no influence on voltage-sensitive sodium/potassium channels in snail and rat dorsal root ganglion (DRG) neurons, nor on a variety of cloned voltage-gated ion channels. The toxin sequence was fully elucidated by Edman degradation. PhcrTx2 is a new β-defensin-fold peptide that shares a sequence similarity to type 3 potassium channels toxins. However, its low activity on the evaluated ion channels suggests that its molecular target remains unknown. PhcrTx2 is the first known paralyzing toxin in the family Phymanthidae.