Figure 4.

Cytotoxic action of ricin on cells. Binding to cytosolic chaperones, ribosome-mediated refolding and interactions with ribosomal and proteasomal factors are pathways by which ricin A-chain can obtain its active form. However, ricin A-chain is partially degraded by proteasomes. Active ricin A-chain is an N-glycosidase that removes a universally-conserved adenine at position 4324 from the α–sarcin-ricin loop (SRL) of the rRNA present in the large ribosomal subunit. The interaction of ricin A-chain with the large ribosomal subunit is facilitated by the ribosomal stalk structure, composed of P0, P1 and P2 proteins. The damage of the 28S rRNA by ricin leads to the inhibition of protein synthesis and triggers the ribotoxic stress response (RSR). Both pathways can induce apoptosis and further inflammation. Ricin A-chain can also directly induce DNA damage. Yeast proteins are shown in magenta; mammalian proteins are shown in black. 20S refers to the core particle, whereas 19S refers to the regulatory particle of the proteasome. For a detailed description, please see the text.