Fungal Ribotoxins

Abstract

Fungal ribotoxins constitute a family of extracellular ribonucleases with exquisite specificity against rRNA (ribonucleic acid). They induce apoptotic death of cells after inhibiting protein translation. Ribosomes become functionally incompetent because ribotoxins cleave one single phosphodiester bond, located at a unique and universally conserved loop, needed for elongation factors function. As secreted proteins, ribotoxins need to cross the membrane of their target cells in order to exert their catalytic activity, and they do it without receptor mediation. Using lipid model systems, it has been shown that they are able to enter cells with membranes enriched in acidic phospholipids. Both membrane‐interacting and ribosomal‐recognition activities are characterised by distinct structural features. Even though the natural function of ribotoxins is not known yet, their production by entomopathogenic fungi has suggested their insecticidal role. After decades of detailed study, the biotechnological potential of ribotoxins in pest control and as antitumour agents is becoming evident. Key Concepts Ribotoxins are extremely specific ribonucleases targeted against ribosomes. Ribotoxins are produced by fungi, some of them entomopathogens. They show a high degree of structural conservation, including the local arrangement of the active site residues. Cleavage of a single rRNA phosphodiester bond leads to cell death by inhibiting translation. Ribotoxins are cyclising RNases because they follow a general acid–base mechanism with production of a 2′,3′‐cyclic intermediate. Ribotoxins must first enter their target cells to exert their lethal action. Cell entrance is possible in cells with membranes enriched in acidic phospholipids and altered permeability. Ribotoxins are optimal candidates to be employed as pest control agents and in antitumour immunotoxins.

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