Core Facility Functional Peptidomics, Ulm University Medical Center, Albert-Einstein-Allee 47, 89081 Ulm, Germany.
Department of Experimental and Clinical Peptide Chemistry, Hannover Medical School (MHH), Feodor-Lynen-Straße 31, D-30625 Hannover, Germany.
Toxins (Basel). 2018 Feb 7;10(2):72. doi: 10.3390/toxins10020072.
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. 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 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%, IC 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.
海葵产生蛋白毒素用于捕食和防御，包括作用于多种药理学和生物医学感兴趣的离子通道的肽毒素。 通常在加勒比海发现;然而，除了 PhcrTx1 之外，其毒素的化学结构和生物活性仍然未知，PhcrTx1 是一种酸感应离子通道 (ASIC) 抑制剂。因此，在本工作中，我们专注于通过色谱分离来分离和表征新的 毒素，然后对螃蟹进行毒性筛选，评估离子通道，并进行序列分析。发现了五组有毒的色谱馏分，纯化并命名为 PhcrTx2 的新的麻痹毒素。该毒素抑制蜗牛神经元中的谷氨酸门控电流（最大抑制 35%，IC 4.7 µM），并且对蜗牛和大鼠背根神经节 (DRG) 神经元中的电压敏感钠/钾通道几乎没有影响，也对各种克隆的电压门控离子通道没有影响。毒素序列通过 Edman 降解完全阐明。PhcrTx2 是一种新的β-防御素折叠肽，与 3 型钾通道毒素具有序列相似性。然而，其对评估离子通道的低活性表明其分子靶标仍未知。PhcrTx2 是 Phymanthidae 家族中已知的第一个麻痹毒素。
