Fungal ribotoxins: structure, function and evolution

Abstract

Ribotoxins are a family of fungal extracellular ribonucleases which inactivate ribosomes by specifically cleaving a single phosphodiester bond located at the universally conserved sarcin/ricin loop of the large rRNA. The subsequent inhibition of protein biosynthesis is followed by cell death via apoptosis. Ribotoxins are also able to interact with membranes containing acid phospholipids, their cytotoxicity being preferentially directed towards cells showing altered membrane permeability, e.g. transformed or virus infected cells. Many features of their cytotoxic action and their ribonucleolytic mechanism have been elucidated by comparison with other extracellular non toxic fungal RNases, best represented by RNase T1. The study of structure-function relationships in ribotoxins is of particular interest, since they are postulated as potential therapeutic agents against different human pathologies. The production of hypoallergenic variants with application in several Aspergillus-related allergic syndromes and the construction of immunotoxins against different carcinomas are promising examples of such potential therapeutic utilisation.