RT Journal Article T1 Involvement of loops 2 and 3 of alpha-sarcin on its ribotoxic activity A1 Castaño Rodríguez, Carlos A1 Olombrada Sacristán, Miriam A1 Partida Hanon, Angélica A1 Lacadena García-Gallo, Francisco Javier A1 Oñaderra Sánchez, Mercedes A1 Gavilanes, José G. A1 García Ortega, Lucía A1 Martínez Del Pozo, Álvaro AB Ribotoxins are a family of fungal ribosome-inactivating proteins displaying highly specific ribonucleolytic activity against the sarcin/ricin loop (SRL) of the larger rRNA, with a-sarcin as its best-characterized member. Their toxicity arises from the combination of this activity with their ability to cross cell membranes. The involvement of a-sarcin's loops 2 and 3 in SRL and ribosomal proteins recognition, as well as in the ribotoxin-lipid interactions involving cell penetration, has been suggested some time ago.In the work presented now different mutants have been prepared in order to study the role of these loops in their ribonucleolytic and lipid-interacting properties. The results obtained confirm that loop 3 residues Lys 111, 112, and 114 are key actors of the specific recognition of the SRL. In addition, it is also shown that Lys 114 and Tyr 48 conform a network of interactions which is essential for the catalysis. Lipid-interaction studies show that this Lys-rich region is indeed involved in the phospholipids recognition needed to cross cell membranes. Loop 2 is shown to be responsible for the conformational change which exposes the region establishing hydrophobic interactions with the membrane inner leaflets and eases penetration of ribotoxins target cells. PB Elsevier SN 0041-0101 YR 2015 FD 2015 LK https://hdl.handle.net/20.500.14352/33752 UL https://hdl.handle.net/20.500.14352/33752 LA eng NO Ministerio de Economía y Competitividad de España NO Campus de Excelencia Internacional Moncloa - PICATA DS Docta Complutense RD 27 dic 2025