Ribosome-inactivating proteins Potent poisons and molecular tools

• Published in: Virulence Vol. 4; no. 8; pp. 774 - 784
• Main Authors: Walsh, Matthew J, Dodd, Jennifer E, Hautbergue, Guillaume M
• Format: Journal Article
• Language: English
• Published: United States Taylor & Francis 15.11.2013; Landes Bioscience
• Subjects: abrin; analytical and therapeutic applications; Bacterial Toxins - metabolism; biological weapon; BLF1; BPSL1549; eukaryotic protein synthesis inhibition; Humans; Poisons - toxicity; Protein Synthesis Inhibitors - toxicity; Ribosome Inactivating Proteins - toxicity; ricin; RNA, Ribosomal, 28S - metabolism; saporin; Shiga toxins; Special Focus Review; α-sarcin; abrin; biological weapon; ricin; BPSL1549; analytical and therapeutic applications; α-sarcin; BLF1; Shiga toxins; saporin; eukaryotic protein synthesis inhibition
• ISSN: 2150-5594; 2150-5608
• DOI: 10.4161/viru.26399

Ribosome-inactivating proteins (RIPs) were first isolated over a century ago and have been shown to be catalytic toxins that irreversibly inactivate protein synthesis. Elucidation of atomic structures and molecular mechanism has revealed these proteins to be a diverse group subdivided into two classes. RIPs have been shown to exhibit RNA N-glycosidase activity and depurinate the 28S rRNA of the eukaryotic 60S ribosomal subunit. In this review, we compare archetypal RIP family members with other potent toxins that abolish protein synthesis: the fungal ribotoxins which directly cleave the 28S rRNA and the newly discovered Burkholderia lethal factor 1 (BLF1). BLF1 presents additional challenges to the current classification system since, like the ribotoxins, it does not possess RNA N-glycosidase activity but does irreversibly inactivate ribosomes. We further discuss whether the RIP classification should be broadened to include toxins achieving irreversible ribosome inactivation with similar turnovers to RIPs, but through different enzymatic mechanisms.