Department of Plant Sciences, George S. Wise Faculty of Life Sciences, Tel Aviv University, Ramat Aviv, Tel Aviv 69978, Israel.
Toxicon. 2009 Dec 15;54(8):1089-101. doi: 10.1016/j.toxicon.2009.02.028. Epub 2009 Mar 5.
The venom of sea anemones is rich in low molecular weight proteinaceous neurotoxins that vary greatly in structure, site of action, and phyletic (insect, crustacean or vertebrate) preference. This toxic versatility likely contributes to the ability of these sessile animals to inhabit marine environments co-habited by a variety of mobile predators. Among these toxins, those that show prominent activity at voltage-gated sodium channels and are critical in predation and defense, have been extensively studied for more than three decades. These studies initially focused on the discovery of new toxins, determination of their covalent and folded structures, understanding of their mechanisms of action on different sodium channels, and identification of the primary sites of interaction of the toxins with their channel receptors. The channel binding site for Type I and the structurally unrelated Type III sea anemone toxins was identified as neurotoxin receptor site 3, a site previously shown to be targeted by scorpion alpha-toxins. The bioactive surfaces of toxin representatives from these two sea anemone types have been characterized by mutagenesis. These analyses pointed to heterogeneity of receptor site 3 at various sodium channels. A turning point in evolutionary studies of sea anemone toxins was the recent release of the genome sequence of Nematostella vectensis, which enabled analysis of the genomic organization of the corresponding genes. This analysis demonstrated that Type I toxins in Nematostella and other species are encoded by gene families and suggested that these genes developed by concerted evolution. The current review provides a brief historical description of the discovery and characterization of sea anemone toxins that affect voltage-gated sodium channels and delineates recent advances in the study of their structure-activity relationship and evolution.
海葵毒液富含低分子量蛋白神经毒素，这些毒素在结构、作用部位和系统发生（昆虫、甲壳类或脊椎动物）偏好上有很大差异。这种毒性的多样性可能有助于这些固着动物栖息在各种移动捕食者共同栖息的海洋环境中。在这些毒素中，那些在电压门控钠离子通道中表现出显著活性的毒素，对于捕食和防御至关重要，已经被广泛研究了三十多年。这些研究最初集中在发现新的毒素、确定它们的共价和折叠结构、了解它们在不同钠离子通道上的作用机制，以及确定毒素与通道受体相互作用的主要部位。I 型和结构上不相关的 III 型海葵毒素的通道结合位点被确定为神经毒素受体 3 位点，该位点以前被证明是蝎子α-毒素的靶标。这两种海葵类型的毒素代表物的生物活性表面已通过诱变进行了表征。这些分析表明，受体 3 位点在各种钠离子通道中存在异质性。海葵毒素进化研究的一个转折点是 Nematostella vectensis 基因组序列的最近发布，这使得相应基因的基因组组织分析成为可能。该分析表明，Nematostella 和其他物种中的 I 型毒素由基因家族编码，并表明这些基因是通过协同进化发展而来的。目前的综述简要描述了发现和表征影响电压门控钠离子通道的海葵毒素的历史，并概述了其结构-活性关系和进化研究的最新进展。
