Glycoproteins - Hughes, R. 1985

Functions
Lectins: Carbohydrate-Binding Proteins
Toxic Lectins

Ricin is one of the most potent known toxins, and even microscopic doses are capable of killing a human being. In 1979, on a London street, Georgi Markov, a Bulgarian radio broadcaster, was shot and killed—presumably for political reasons. A hollow pellet was recovered from his body. Judging by its dimensions, there were only two poisons that could fit inside it in a quantity sufficient to cause death. One of them was ricin, and indeed, it was detected during the autopsy.

On a more positive note, ricin serves as a highly valuable tool for studying glycoprotein function and, in particular, for elucidating the mechanisms by which Cells internalize small Proteins such as Hormones. Ricin binds to Cell-surface CARBOHYDRATES via its B-subunit (Fig. 4.4). As previously discussed, cell receptors are galactose-containing carbohydrate chains. Ricin then enters the Cytoplasm, where it dissociates into its constituent subunits. The A-subunit binds to Ribosomes and inhibits Protein Synthesis. The complete cessation of cytoplasmic protein synthesis requires the presence of only a few ricin molecules, presumably because the A-subunit catalytically inactivates a ribosomal factor or factors. Several Other toxins with similar Mechanisms of action are also known. All of these toxins consist of two distinct subunits: one binds to cell-surface receptors, while the other disrupts a vital metabolic process, thereby killing the susceptible cell. The toxic lectin abrin (from the seeds of Abrus precatorius) binds to the same sites as ricin and inhibits protein synthesis, whereas modeccin—a lectin from Adenia digitata—also binds to galactose-containing receptors. One of the two subunits of diphtheria toxin specifically interacts with Glycoproteins, while the other, toxic subunit halts protein synthesis by interfering with The transfer of the ADP-ribosyl group from NAD⁺ to elongation factor 2 (EF2). Although the precise intracellular sites of action for other Lectins have not yet been fully established, it is clear that in all cases, binding to carbohydrate receptors is a necessary initial step, and that one of the factors contributing to cytotoxicity is the inhibition of nutrient Transport Across the membrane.

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Fig. 4.4. MECHANISM OF ACTION of ricin.