Modeccin is a toxic lectin, a group of glycoproteins capable of binding specifically to sugar moieties.
[1][2] Modeccin consists of two subunits that are bound by a disulfide linkage, the intact protein has a molecular weight of approximately 57-63 kDa.
Reduced, dissociated toxin subunits inhibit ribosomal activity in cell-free systems, but they have no effect on intact cells.
Toxin molecules bind through saccharide recognition sites on the B-chain to particular β-galactosyl-containing glycoprotein or glycolipid components on the surface of cell membranes.
Once inside the cell the A-chain enters the cytoplasmic space, binds to the 60S ribosomal subunit and enzymatically inactivates it.
The mechanism is catalytic because of this one toxin molecule is enough to disrupt protein synthesis and kill the target cell.
Hybrid molecules were prepared from the A- and B-chains of the toxic lectins ricin and modeccin by dialyzing mixtures of isolated chains to allow a disulfide bridge to be formed between them.
The bound proteins, including modeccin, were eluted and fractionised using a gradient of sodium chloride in solution.
Affinity was increased by glycoprotein-treatment with neuraminidase, enzymes that cleave glycosidic linkages of neuraminic acids.
Samples were made containing sodium dodecyl sulphate, and in some cases small amounts of mercapto- ethanol.
This confirms that modeccin consists of two protein chains of 28 and 38 kDa respective, linked via a disulfide bond.
The B-chain has saccharide recognition sites for particular ß-galactosyl-containing glycopro-teins or glycolipid compounds on the cell membrane.
[23] A conformational change to the 60S ribosomal subunit is induced by EF2, which is favourable for the action of modeccin B-chain.
[23] Modeccin facilitates destruction of dopaminergic neurons in the ipsilateral substantia nigra and intralaminar thalamus in mice central nervous system (CNS).
Free toxin is removed by primarily the liver and kidneys or may be degraded through cellular internalization via lysosomes.
Brefeldin A blocks transport from the Endoplasmatic Reticulum and inhibits vesicle formation in the Golgi apparatus.
Nucleotide exchange into ADP-ribosylation factor (ARF) is inhibited by BFA, thus preventing assembly of cytosolic coat proteins on target membranes.
The protective effect of ceramide analogs and related sphingolipids, shown in figure 5, is observed in cytotoxin activity of modeccin.