Relationship between elongation factor 1- and elongation factor 2-dependent guanosine triphosphatase activities of ribosomes. Inhibition of both activities by ricin

Abstract

The elongation factor 1- and elongation factor 2-dependent GTPase (guanosine triphosphatase) activities of ribosomes are inhibited by ricin, a toxic protein known to inactivate the 60S ribosomal subunit. It is suggested that also in eukaryotic ribosomes a "GTPase site', located on the larger subunit, is common to the two elongation factors.

Effect of modeccin on the steps of peptide-chain elongation

“…Montanaro et al (1973) and Sperti et al (1975Sperti et al ( , 1976 found that ricin had little influence on the EF 1-and guanine nucleotide-dependent binding of ['4C]-phenylalanyl-tRNA to rat liver and to A. salina ribosomes, and similar results were obtained by Nolan et al (1976) working with ribosomes from Krebs II mouse ascites cells. On the contrary, Carrasco et al (1975) and Fernandez-Puentes et al (1976a) described experiments in which ricin and abrin strongly inhibited the EF 1-and GTP-dependent binding of ["4C]phenylalanyl-tRNA to rabbit reticulocyte ribosomes; they pointed out that the lack of inhibition observed by Montanaro et al (1973) and other workers could depend on either the small proportion of active ribosomes or the saturating concentrations of EF 1 present in the assays.…”

“…As reported above, the study of the effect of ricin and other related plant toxins on the EF 1-dependent binding of aminoacyl-tRNA to ribosomes has given contradictory results (Montanaro et al, 1973;Sperti et al, 1975Sperti et al, , 1976Nolan et al, 1976;Carrasco et al, 1975;Fernandez-Puentes et al, 1976a). In a previous paper from this laboratory (Sperti et al, 1976) it was stated that ricin scarcely affected the EF 1-dependent binding of phenylalanyl-tRNA to A. salina ribosomes.…”

Phytohemagglutinins (Phytolectins)

“…The specific target of ricin is the 60S subunit of the ribosome (37,82,172,252) where it somehow interferes with the process of peptide chain elongation (37,171,187). It has been suggested that the action of ricin may be enzymatic in nature (172,189,192) and that its specific site of reaction may be guanosine triphosphatase (253). Whether or not this suggested enzymatic activity is in any way related to the proteolytic activity reported to be associated with ricin (72) remains to be explored.…”

Inhibition of Neurospora crassa and yeast mitochondrial protein synthesis by ricin, a toxic protein inactive on E. coli protein synthesis

“…The situation might be different in the rat liver system, where an inhibition of mitochondrial protein synthesis by ricin was not observed [9]. Ricin has been shown to interfere with the elongation of already initiated polypeptide chains [ 18,19]. An 8 S complex, consisting of 5 S RNA and L3 protein, obtained by treatment of 60 S mammalian cytoplasmic ribosomes with EDTA [20][21][22] has some GTPase activity [21 ].…”