Abstract | Sea anemones are a rich source of lethal pore-forming peptides and proteins, known collectively as cytolysins or actinoporins. There are several different groups of cytolysins based on their structure and function [11689232]. This entry represents the most numerous group, the 20-kDa highly basic peptides. These cytolysins form cation-selective pores in sphingomyelin-containing membranes. Examples include equinatoxins (from Actinia equina), sticholysins (from Stichodactyla helianthus), magnificalysins (from Heteractis magnifica), and tenebrosins (from Actinia tenebrosa), which exhibit pore-forming, haemolytic, cytotoxic, and heart stimulatory activities.
Cytolysins adopt a stable soluble structure, which undergoes a conformational change when brought in contact with a membrane, leading to an active, membrane-bound form that inserts spontaneously into the membrane. They often oligomerise on the membrane surface, before puncturing the lipid bilayers, causing the cell to lyse. The 20-kDa sea anemone cytolysins require a phosphocholine lipid headgroup for binding, however sphingomyelin is required for the toxin to promote membrane permeability [14604518]. The crystal structures of equinotoxin II [11827489] and sticholysin II [14604522] both revealed a compact beta-sandwich consisting of ten strands in two sheets flanked on each side by two short alpha-helices, which is a similar topology to osmotin. It is believed that the beta sandwich structure attaches to the membrane, while a three-turn alpha helix lying on the surface of the beta sheet may be involved in membrane pore formation, possibly by the penetration of the membrane by the helix.
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