The plant toxin ricin is highly toxic for mammalian cells and is of concern for bioterrorism. Ricin belongs to a family of functionally related toxins, collectively referred to as ribosome inactivating proteins (RIPs), which disable ribosomes and halt protein synthesis. Currently there are no specific antidotes against ricin or related RIPs. The catalytic subunit of ricin is an N-glycosidase that depurinates a universally conserved adenine residue within the sarcin/ricin loop (SRL) of the 28S rRNA. This depurination activity inhibits translation and its biochemistry has been intensively studied. Yet, recent developments paint a more complex picture of toxicity, with ribosomal proteins and cellular signaling pathways contributing to the potency of ricin. In particular, several studies have now established the importance of the ribosomal stalk structure in facilitating the depurination activity and ribosome specificity of ricin and other RIPs. This review highlights recent developments defining toxin–ribosome interactions and examines the significance of these interactions for toxicity and therapeutic intervention.Highlights:
▸ This article summarizes recent developments in the interaction of ricin with ribosomes. ▸ We review the importance of the ribosomal stalk for the activity and specificity of ricin. ▸ We highlight recent developments, which define toxin–ribosome interactions. ▸ We examine the significance of ribosome binding for toxicity and therapeutic intervention.