Ribosome Inactivation
Ricin works by getting inside the cells of a
person’s body and preventing the cells from making the proteins they need.
Without the proteins, cells die, and eventually the whole body can shut down
and die.
Study of the
N-glycosidase activity of ricin was pioneered by Endo and Tsurugi who showed
that RTA cleaves a glycosidic bond within the large rRNA of the 60S subunit of
eukaryotic ribosomes. They subsequently showed RTA specifically and
irreversibly hydrolyses the N-glycosidic bond of the adenine residue at
position 4324 (A4324) within the 28S rRNA, but leaves the phosphodiester
backbone of the RNA intact. The ricin targets A4324 that is contained in a
highly conserved sequence of 12 nucleotides universally found in eukaryotic ribosomes.
The sequence, 5’-AGUACGAGAGGA-3’, termed the sarcin-ricin loop, is important in
binding elongation factors during protein synthesis. The depurination event
rapidly and completely inactivates the ribosome, resulting in toxicity from
inhibited protein synthesis. A single RTA molecule in the cytosol is capable of
depurinating approximately 1500 ribosomes per minute.
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