Alvaro Martinez-Del-Pozo
Universidad Complutense de Madrid, Spain
Transforming a sea anemone pore-forming toxin into a plastic-degrading nanoreactor
Living beings produce toxins in order to predate, or protect themselves. Sessile organisms, such as many plants or fungi, are especially effective in synthesizing and using venoms. Sea anemones are primitive animals with lack the ability to move. Therefore, they store complex venoms in their tentacles, including a family of pore-forming proteins known as actinoporins (1, 2). Even the most basic Biochemistry textbooks sustain the clear-cut classification that distinguishes between soluble and membrane proteins. However, actinoporins constitute a fascinating system of study because they escape to this simple classification. They show a dual behavior at the water-membrane interface. In water solution, actinoporins remain mostly monomeric and stably folded but upon interaction with lipid membranes, they suffer a metamorphosis to become oligomeric integral membrane structures, puncturing the cells, and producing death by osmotic shock. This cytolytic action is triggered by the recognition of sphingomyelin, which behaves as an authentic specific lipid membrane receptor.
Our group aims to study in deep detail the mechanism of action of different toxic proteins with the idea of transforming them into beneficial products. Consequently, we have studied the behavior of several of these actinoporins, including their protein-lipid interactions (3) and the determination of their pore structures (lipids included) with atomic resolution (4). Then, in collaboration with two other Spanish groups, and using nanodiscs platforms, we have modified one of these proteins to convert it into two different multicatalytic nanoreactors, which degrade nano-sized polyethylene terephthalate (PET) particles at 40ºC and pH 7.0 (5). The results obtained suggest that these catalytic nanoreactors are promising tools in nanotechnology for filtering, capturing and breaking down nanoPET particles, for example, in wastewater treatment plants.
References
1. García-Ortega, L.; Alegre-Cebollada, J.; García-Linares, S.; Bruix, M.; Martínez-del-Pozo, A.; Gavilanes, J.G., The behavior of sea anemone actinoporins at the water-membrane interface. Biochim Biophys Acta 2011, 1808 (9), 2275.
2. Palacios-Ortega, J.; García-Linares, S.; Rivera-de-Torre, E.; Heras-Márquez, D.; Gavilanes, J.G.; Slotte, J.P.; Martínez-del-Pozo, A., Structural foundations of sticholysin functionality. Biochim Biophys Acta Proteins Proteom 2021, 140696
3. García-Linares, S.; Rivera-de-Torre, E.; Morante, K.; Tsumoto, K.; Caaveiro, J.M.; Gavilanes, J.G.; Slotte, J.P.; Martínez-del-Pozo, Á., Differential effect of membrane composition on the pore-forming ability of four different sea anemone actinoporins. Biochemistry 2016, 55 (48), 6630
4. Arranz, R.; Santiago, C.; Masiulis, S.; Rivera-de-Torre, E.; Palacios-Ortega, J.; Carlero, D.; Heras-Márquez, D.; Gavilanes, J.G.; Arias-Palomo, E.; Martínez-del-Pozo, Á.; García-Linares, S.; Martín-Benito, J., The action mechanism of actinoporins revealed through the structure of pore-forming intermediates. bioRxiv 2024, doi: https://doi.org/10.1101/2024.06.27.601005
5. Robles-Martín, A.; Amigot-Sánchez, R.; Fernandez-Lopez, L.; Gonzalez-Alfonso, J.L.; Roda, S.; Alcolea-Rodriguez, V.; Heras-Márquez, D.; Almendral, D.; Coscolín, C.; Plou, F.J.; Portela, R.; Bañares, M.A.; Martínez-del-Pozo, A.; García-Linares, S.; Ferrer, M.; Guallar, V., Sub-micro- and nano-sized polyethylene terephthalate deconstruction with engineered protein nanopores. Nat Catal 2023, 6 (12), 1174