Journal
JOURNAL OF BIOCHEMISTRY
Volume 170, Issue 4, Pages 473-482Publisher
OXFORD UNIV PRESS
DOI: 10.1093/jb/mvab062
Keywords
Agrocybe aegerita; calorimetry; liposomes; membrane interactions; ribotoxin-like proteins
Categories
Funding
- University of Naples 'Federico II'
- University of Campania 'Luigi Vanvitelli'
- V: ALERE (VAnviteLli pEr la RicErca) program, investments for research and young people of University of Campania 'Luigi Vanvitelli', by 'DicoVale' project program, Campania region (Italy
- P.S.R. 2014-2020
- Typology 10.2.1.)
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Ageritin is a prototype of a new ribotoxin-like protein family that has selective toxicity towards cancer cells, possibly due to its interaction with anionic lipids.
Ageritin is the prototype of a new ribotoxin-like protein family, which has been recently identified also in basidiomycetes. The protein exhibits specific RNase activity through the cleavage of a single phosphodiester bond located at sarcin/ricin loop of the large rRNA, thus inhibiting protein biosynthesis at early stages. Conversely to other ribotoxins, its activity requires the presence of divalent cations. In the present study, we report the activity of Ageritin on both prokaryotic and eukaryotic cells showing that the protein has a prominent effect on cancer cells viability and no effects on eukaryotic and bacterial cells. In order to rationalize these findings, the ability of the protein to interact with various liposomes mimicking normal, cancer and bacterial cell membranes was explored. The collected results indicate that Ageritin can interact with DPPC/DPPS/Chol vesicles, used as a model of cancer cell membranes, and with DPPC/DPPG vesicles, used as a model of bacterial cell membranes, suggesting a selective interaction with anionic lipids. However, a different perturbation of the two model membranes, mediated by cholesterol redistribution, was observed and this might be at the basis of Ageritin selective toxicity towards cancer cells.
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