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Involvement of loops 2 and 3 of alpha-sarcin on its ribotoxic activity

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Castaño Rodríguez, Carlos and Olombrada Sacristán, Miriam and Partida Hanon, Angélica and Lacadena García-Gallo, Javier and Oñaderra Sánchez, Mercedes and Gavilanes Franco, José G. and García Ortega, Lucía and Martínez del Pozo, Álvaro (2015) Involvement of loops 2 and 3 of alpha-sarcin on its ribotoxic activity. Toxicon, 96 . pp. 1-9. ISSN 0041-0101

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Official URL: http://www.sciencedirect.com/science/article/pii/S0041010115000100



Abstract

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.


Item Type:Article
Uncontrolled Keywords:Ribotoxin, Cation-π interaction, SRL, Lys-rich region
Subjects:Medical sciences > Biology > Biochemistry
ID Code:28113
Deposited On:28 Jan 2015 15:56
Last Modified:28 Jan 2015 15:56

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