Ribosome inactivating proteins: Enzymes in search of biological function

Ribosome-inactivating proteins (RIPs) are enzymes (N-glycosidases classified as rRNA N-glycohydrolases, EC 3.2.2.22), mostly of plant origin, but also of bacterial, fungal and algal origin, which cause irreversible inhibition of protein biosynthesis carried out by ribosomes of superior organisms and some bacteria. The enzymatic activity consists of specific depurination of ribosomes that renders them unable to interact with elongation factor 2 in eukaryotes and elongation factor G in prokaryotes. The best-known RIPs, ricin and abrin, consisting of two polypeptide chains (type 2), an enzymatic chain and a lectin chain specific for D-galactose and galactosides, are extremely toxic because they can be internalised in cells by binding to plasma membrane receptors, entering the cytoplasm, reaching the Golgi apparatus, and then reaching the rough endoplasmic reticulum, where they are transferred to the cytosol and there inactivate ribosomes. The most abundant RIPs possess only one enzymatic chain (type 1) and do not possess the toxicity of ricin and abrin. Their biological function in plants is currently unknown, although different hypotheses have been proposed for their mediation in plant stress response and against pathogens. RIPs have found an interesting application in the construction of immunotoxins and conjugates in experimental cancer therapy. The formulation of RIPs into nanoparticles, has been used to optimize their biopharmaceutical and pharmacokinetic properties and for diagnostic purposes. Keywords: RIP; enzyme; function; inmunotoxin; drug targeting