Modeccin — A plant toxin inhibiting protein synthesis

Refsnes, Karin; Haylett, Thomas; Sandvig, Kirsten; Olsnes, Sjur

doi:10.1016/0006-291x(77)91130-5

Cited by 52 publications

(21 citation statements)

References 3 publications

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“…It is clear that one toxin molecule inactivated several ribosomes in agreement with previous results [8]. Altogether the data indicate that modeccin acts directly on the ribosomes in a catalytic way, most likely by exhibiting enzymatic activity.…”

Section: Evidence For Enzymatic Inactivation Of Ribosomes By Modeccinsupporting

confidence: 90%

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

Olsnes

Abraham

1979

European Journal of Biochemistry

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Isolated rabbit reticulocyte ribosomes were treated with the toxic lectin modeccin for increasing periods of time. The toxin treatment was stopped by adding specific antitoxin and the residual activity of the ribosomes was tested in a polyphenylalanine-synthesizing system.With increasing time of toxin treatment the ability of the ribosomes to support polymerization of phenylalanine decreased. Addition of anti-toxin immediately stopped further inactivation of the ribosomes. The presence of elongation factor 2 (EF-2) strongly increased the rate of ribosome inactivation by modeccin. There was no similar effect with EF-1. Maximal rate of inactivation was observed when the molar ratio of EF-2 to ribosomes was about 1. The rate of ribosome inactivation was about 4 ribosomes min-l (molecule of modeccin)-' under optimal conditions. The ability of EF-2 to sensitize ribosomes to modeccin was strongly descreased in the presence of GTP, G D P and guanosine 5'-[fl,y-methylene]triphosphate. EF-2, which had been ADP-ribosylated in the presence of diphtheria toxin, was fully active in sensitizing the ribosomes whereas N-ethylmaleimide-treated EF-2 had lost this ability.Isolated 60-S subunits were sensitized to modeccin by EF-2 in a similar way as whole ribosomes.The data indicate that modeccin inactivates ribosomes catalytically and that in the absence of nucleotides it binds to the 60-S subunit in a specific way. The possibility of two binding sites for EF-2 on the ribosomes is discussed.

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Section: Evidence For Enzymatic Inactivation Of Ribosomes By Modeccinsupporting

confidence: 90%

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

Olsnes

Abraham

1979

European Journal of Biochemistry

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“…Part of the material was then dialyzed for four days against several shifts of distilled water at 4" to allow reoxidation to take place. Increasing amounts of the different preparations were added to HeLa cells growing in Linbro trays FB-16-24-TC, and the incorporation of [ ''C]-leucine was measured after 14 h as described previously [2]. A) reduced modeccin; 0 ) reduced and dialyzed modeccin; X ) untreated modeccin.…”

Section: Resultsmentioning

confidence: 99%

“…The increased sensitivity to abrin and ricin was associated with an increase in the total number of binding sites for abrin (Table 111). We have earlier shown that neuraminidase treatment of the parent HeLa cells increased their sensitivity to modeccin about 10-fold [ 2 ] . The data in Table 111 show that the number of binding sites on these cells increased by the same factor.…”

Section: Ts:113mentioning

confidence: 93%

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

Olsnes

Sandvig²,

Eiklid

et al. 1978

J Supramol Struct

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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.

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“…This was initially shown for diphtheria toxin [9] and, subsequently, the plant toxins abrin and ricin [39,40] and the bacterial cholera toxin [19] were shown to act in the cytosol. Later the plant toxins modeccin [45], viscumin [62], and volkensin [63], and the bacterial Pseudomonas aeruginosa exotoxin A [24], Shigella (or Shiga) toxin [4,46], Shiga-like toxins [14], E. coli heatlabile toxin [20], pertussis toxin [64], anthrax toxin [26], Bordetella pertussis invasive adenylate cyclase [22], tetanus and botulinum toxins [58] have been shown to act in a direct way on targets in the cytosol. In addition there are a number of candidate toxins where intracellular action is likely, although this has not been clearly demonstrated up to now [21,23,47].…”

Section: Introductionmentioning

confidence: 99%