2026-06-26T20:32:05Zhttps://docta.ucm.es/rest/oai/request

oai:docta.ucm.es:20.500.14352/182632024-09-23T17:59:24Zcom_20.500.14352_14col_20.500.14352_15

Rivera de Torre, Esperanza Palacios Ortega, Juan García Linares, Sara Gavilanes, José G. Martínez Del Pozo, Álvaro 2023-06-17T22:14:34Z 2023-06-17T22:14:34Z 2017-12 10.1016/j.abb.2017.11.005 https://hdl.handle.net/20.500.14352/18263 http://www.sciencedirect.com/science/article/pii/S000398611730632X?via%3Dihub Sticholysins I and II (StnI and StnII), α-pore forming toxins from the sea anemone Stichodactyla helianthus, are water-soluble toxic proteins which upon interaction with lipid membranes of specific composition bind to the bilayer, extend and insert their N-terminal α-helix, and become oligomeric integral membrane structures. The result is a pore that leads to cell death by osmotic shock. StnI and StnII show 93% of sequence identity, but also different membrane pore-forming activities. The hydrophobicity profile along the first 18 residues revealed differences which were canceled by substituting StnI amino acids 2 and 9. Accordingly, the StnID9A mutant, and the corresponding StnIE2AD9A variant, showed enhanced hemolytic activity. They also revealed a key role for an exposed salt bridge between Asp9 and Lys68. This interaction is not possible in StnII but appears conserved in the other two well-characterized actinoporins, equinatoxin II and fragaceatoxin C. The StnII mutant A8D showed that this single replacement was enough to transform StnII into a version with impaired pore-forming activity. Overall, the results show the key importance of this salt bridge linking the N-terminal stretch to the β-sandwich core. A conclusion of general application for the understanding of salt bridges role in protein design, folding and stability. eng restricted access One single salt bridge explains the different cytolytic activities shown by actinoporins sticholysin I and II from the venom of Stichodactyla helianthus journal article