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 α-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.
Bibliographical noteFunding Information:
The work conducted at Tel Aviv University was supported by the United States-Israel Binational Agricultural Research and Development grants IS-3928-06 (M.G. and D.G.) and IS-4066-07 (D.G. and M.G.); by the Israeli Science Foundation grants 107/08 (M.G.) and 1008/05 (D.G. and M.G.); by the European Community Integrated Project LSH-2005-1.2.5-2 proposal No. 037592 - CONCO (M.G. and D.G.); and by NIH 1 U01 NS058039-01 (M.G.)
- Molecular evolution
- Sea anemone
- Structure-function relationship
- Voltage-gated sodium channels