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Sticholysins are pore-forming toxins produced by the sea anemone Stichodactyla helianthus. When they encounter a sphingomyelin-containing membrane, these proteins bind to it and oligomerize, a process that ends in pore formation. Mounting evidence indicates that StnII can favour the activity of StnI. Previous results have shown that these two isotoxins can oligomerize together. Furthermore, StnII appeared to potentiate the activity of StnI through the membrane-binding step of the process. Hence, isotoxin interaction should occur prior to membrane encounter. Here, we have used analytical ultracentrifugation to investigate the oligomerization of Stns in solution, both separately and together. Our results indicate that while StnI seems to be more prone to oligomerize in water solution than StnII, a small percentage of StnII in StnI-StnII mixtures promotes oligomerization.

The usefulness of toxicity across the tree of life is far beyond doubt. Most, if not all, organisms produce compounds that can be used for attack and/or defense against external entities. Some of the most specialized of these compounds are toxic proteins, among which pore-forming toxins (PFTs) particularly excel. PFTs are present in all kingdoms of life. Given the wide variety of PFTs, one can expect a multitude of different specificities and mechanisms of action, of which we will certainly take advantage at some point. For that, a thorough characterization of PFTs and their functionality is necessary. In this thesis, we have taken further the characterization of sticholysins, small PFTs produced by the sea anemone Stichodactyla helianthus..., La toxicidad es indudablemente útil para los seres vivos. La mayoría, si no todos los organismos, producen compuestos para usarlos contra otros seres vivos, ya sea confines de defensa o de ataque. Algunos de los más especializados de estos compuestos son las proteínas tóxicas, entre las que destacan las toxinas formadoras de poros (ing.,pore-forming toxins, PFT). Estas proteínas pueden encontrarse en todos los reinos dela vida. Dada su amplia diversidad, puede esperarse que tengan una gran variedad de especificidades y mecanismos de acción. Una caracterización detallada de las PFT y su funcionalidad es un requisito fundamental para, en un futuro, poder beneficiarse dela acción de estas toxinas. Por ello, en esta tesis se ha profundizado en el comportamiento de las esticolisinas, pequeñas PFT producidas por la anémona del mar Caribe Stichodactyla helianthus..., Nyttan av toxicitet hos olika organismer är långt bortom tvivel. De flesta, om inte alla,organismer producerar föreningar som kan användas för attack och/eller försvar motexterna hot. Några av de mest specialiserade av dessa föreningar är toxiska proteiner,bland vilka por-bildande toxiner (eng., pore-forming toxins, PFT) är särskiltutmärkande. PFT finns i alla livets riken. Med tanke på det stora utbudet av PFT kanman förvänta sig en mängd olika specificiteter och verkningsmekanismer, som vi kankomma att dra nytta i olika tillämpningar. Därför är en grundlig karakterisering avPFT-peptider och deras funktionalitet nödvändig. I denna avhandling har viundersökt och karakteriser olika stickolysiner, vilka är små PFT-peptider produceradeav havsanemonen Stichodactyla helianthus...

Venoms constitute complex mixtures of many different molecules arising from evolution in processes driven by continuous prey–predator interactions. One of the most common compounds in these venomous cocktails are pore-forming proteins, a family of toxins whose activity relies on the disruption of the plasmatic membranes by forming pores. The venom of sea anemones, belonging to the oldest lineage of venomous animals, contains a large amount of a characteristic group of pore-forming proteins known as actinoporins. They bind specifically to sphingomyelin-containing membranes and suffer a conformational metamorphosis that drives them to make pores. This event usually leads cells to death by osmotic shock. Sticholysins are the actinoporins produced by Stichodactyla helianthus. Three different isotoxins are known: Sticholysins I, II, and III. They share very similar amino acid sequence and three-dimensional structure but display different behavior in terms of lytic activity and ability to interact with cholesterol, an important lipid component of vertebrate membranes. In addition, sticholysins can act in synergy when exerting their toxin action. The subtle, but important, molecular nuances that explain their different behavior are described and discussed throughout the text. Improving our knowledge about sticholysins behavior is important for eventually developing them into biotechnological tools.