RT Journal Article T1 The interaction of the ribotoxin α-sarcin with complex model lipid vesicles A1 García Montoya, Carmen A1 García Linares, Sara A1 Heras Márquez, Diego A1 Majnik, Manca A1 Laxalde Fernández, Diego A1 Amigot Sánchez, Rafael A1 Martínez Del Pozo, Álvaro A1 Palacios Ortega, Juan AB Fungal ribotoxins are extracellular RNases that inactivate ribosomes by cleaving a single phosphodiester bond at the universally conserved sarcin-ricin loop of the large rRNA. However, to reach the ribosomes, they need to cross the plasma membrane. It is there where these toxins show their cellular specificity, being especially active against tumoral or virus-infected cells. Previous studies have shown that fungal ribotoxins interact with negatively charged membranes, typically containing phosphatidylserine or phosphatidylglycerol. This ability is rooted on their long, non-structured, positively charged loops, and its N-terminal β-hairpin. However, its effect on complex lipid mixtures, including sphingophospholipids or cholesterol, remains poorly studied. Here, wild-type α-sarcin was used to evaluate its interaction with a variety of membranes not assayed before, which resemble much more closely mammalian cell membranes. The results confirm that α-sarcin is particularly sensitive to charge density on the vesicle surface. Its ability to induce vesicle aggregation is strongly influenced by both the lipid headgroup and the degree of saturation of the fatty acid chains. Acyl chain length is indeed particularly important for lipid mixing. Finally, cholesterol plays an important role in diluting the concentration of available negative charges and modulates the ability of α-sarcin to cross the membrane. PB Elsevier YR 2023 FD 2023-11-23 LK https://hdl.handle.net/20.500.14352/112143 UL https://hdl.handle.net/20.500.14352/112143 LA eng NO Carmen García-Montoya, Sara García-Linares, Diego Heras-Márquez, Manca Majnik, Diego Laxalde-Fernández, Rafael Amigot-Sánchez, Álvaro Martínez-del-Pozo, Juan Palacios-Ortega, The interaction of the ribotoxin α-sarcin with complex model lipid vesicles, Archives of Biochemistry and Biophysics, Volume 751, 2024, 109836, ISSN 0003-9861, https://doi.org/10.1016/j.abb.2023.109836. (https://www.sciencedirect.com/science/article/pii/S0003986123003351) NO Comunidad de Madrid NO Universidad Complutense de Madrid NO Banco Santander DS Docta Complutense RD 8 abr 2025