Ribosome-inactivating proteins: potent poisons and molecular tools.
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.
RNA Biology Laboratory; Sheffield Institute for Translational Neuroscience (SITraN); Department of Neuroscience; University of Sheffield; Sheffield, UK.
Matthew J
MJ
Walsh
RNA Biology Laboratory; Sheffield Institute for Translational Neuroscience (SITraN); Department of Neuroscience; University of Sheffield; Sheffield, UK.
Jennifer E
JE
Dodd
RNA Biology Laboratory; Sheffield Institute for Translational Neuroscience (SITraN); Department of Neuroscience; University of Sheffield; Sheffield, UK.
Guillaume M
GM
Hautbergue
D001427:Bacterial Toxins / Q000378:metabolism; D006801:Humans; D011042:Poisons / Q000633:toxicity*; D011500:Protein Synthesis Inhibitors / Q000633:toxicity*; D012339:RNA, Ribosomal, 28S / Q000378:metabolism; D054788:Ribosome Inactivating Proteins / Q000633:toxicity*
C572779:BLF1 toxin, Burkholderia pseudomallei; D001427:Bacterial Toxins; D011042:Poisons; D011500:Protein Synthesis Inhibitors; D012339:RNA, Ribosomal, 28S; D054788:Ribosome Inactivating Proteins
BLF1; BPSL1549; Shiga toxins; abrin; analytical and therapeutic applications; biological weapon; eukaryotic protein synthesis inhibition; ricin; saporin; α-sarcin