Properties and action mechanism of the toxic lectin modeccin: Interaction with cell lines resistant to modeccin, abrin, and ricin

Abstract

The toxic lectin modeccin, which inhibits protein synthesis in eukaryotic cells, is cleaved upon treatment with 2-mercaptoethanol into two peptide chains which move in polyacrylamide gels at rates corresponding to molecular weights 28,000 and 38,000. After reduction, the toxin loses its effect on cells, while its ability to inhibit cell-free protein synthesis increases. Like abrin and ricin it inhibits protein synthesis by inactivating the 60S ribosomal subunits. Modeccin binds to surface receptors containing terminal galactose residues. Competition experiments with various glycoproteins indicate that the modeccin receptors are different from the abrin receptors. In addition, they were present on HeLa cells in much smaller numbers. Moreover, mutant lines resistant to abrin and ricin were not resistant to modeccin and vice-versa. The toxin resistance of various mutant cell lines could not be accounted for by a reduced number of binding sites on cells. The data are consistent with the view that the cells possess different populations of binding sites with differences in ability to facilitate the uptake of the toxins and that in the resistant lines the most active receptors have been reduced or eliminated.

A Neutralizing Antibody to the A Chain of Abrin Inhibits Abrin Toxicity both In Vitro and In Vivo

“…Abrin is one of the most powerful plant toxins known (28,25). The reported IC 50 for protein synthesis by abrin in cultured cell lines is ϳ0.4 ng/ml (23), and the LD 50 for mice is ϳ0.04 g/kg (35).…”

“…Abrin is an AB type toxin with a 30-kDa A chain, an RNA N-glycosidase that irreversibly inactivates the 28S rRNA of the mammalian 60S ribosomal subunit. Once in the cytosol, the A chain depurinates the adenine of the alpha-sarcin-ricin loop and thereby arrests host cell protein synthesis (7,28). The B chain is a galactose-specific lectin and hence binds to cell surface glycosylated receptors, which allows the toxin entry (31, 16).…”

“…Apart from inhibiting protein synthesis, RIPs induce apoptosis (23). Abrin shows significant similarities to ricin at the sequence level as well as the structural level, but abrin is several times more potent than ricin (28). There is much interest in understanding the bioactivities of these proteins, owing to their extreme toxicity (the 50% lethal dose [LD 50 ] of abrin for mice is 0.04 g/kg of body weight, and the LD 50 of ricin is 3 g/kg) (35), stability, and easy availability.…”

Elongation‐Factor‐2‐Induced Sensitization of Ribosomes to Modeccin

“…Modeccin has many properties in common with abrin and ricin [S-121. Thus, all three toxins consist of two dissimilar peptide chains and bind to cell surface receptors containing terminal galactose, and they all exert their toxicity by inactivating the 60-S ribosomal subunits [12,13]. On the other hand, there are also differences.…”

“…On the other hand, there are also differences. Whereas abrin and ricin appear to bind to the same group of surface receptors, modeccin binds to a different group [12]. Furthermore, modeccin, which is much more active than abrin and ricin in inhibiting protein synthesis in intact cells, is much less active in cell-free systems [12].…”