Abstract
Ricin can be isolated from the seeds of the castor bean plant (Ricinus communis). It belongs to the ribosome-inactivating protein (RIP) family of toxins classified as a bio-threat agent due to its high toxicity, stability and availability. Ricin is a typical A-B toxin consisting of a single enzymatic A subunit (RTA) and a binding B subunit (RTB) joined by a single disulfide bond. RTA possesses an RNA N-glycosidase activity; it cleaves ribosomal RNA leading to the inhibition of protein synthesis. However, the mechanism of ricin-mediated cell death is quite complex, as a growing number of studies demonstrate that the inhibition of protein synthesis is not always correlated with long term ricin toxicity. To exert its cytotoxic effect, ricin A-chain has to be transported to the cytosol of the host cell. This translocation is preceded by endocytic uptake of the toxin and retrograde traffic through the trans-Golgi network (TGN) and the endoplasmic reticulum (ER). In this article, we describe intracellular trafficking of ricin with particular emphasis on host cell factors that facilitate this transport and contribute to ricin cytotoxicity in mammalian and yeast cells. The current understanding of the mechanisms of ricin-mediated cell death is discussed as well. We also comment on recent reports presenting medical applications for ricin and progress associated with the development of vaccines against this toxin.
Highlights
The toxin ricin is a naturally occurring, extremely toxic protein isolated from the seeds of the castor plant, Ricinus communis
EDEM proteins can recognize glycan residues present on their substrates but can bind other structures, e.g., hydrophobic regions or unfolded motifs. This second option seems to be important for EDEMs–ricin interactions since recombinant ricin expressed in E. coli that was used in the experiments, lacks oligosaccharides that are normally added to ricin A-chain derived from plants [140]
Despite the very effective ricin-mediated rRNA depurination event that results in the inhibition of protein synthesis, it cannot be stated that these processes by themselves lead to cell death [24,30,31,32,33,203]
Summary
The toxin ricin is a naturally occurring, extremely toxic protein isolated from the seeds of the castor plant, Ricinus communis. Toxins 2019, 11, 350 of ricin was described by Olsnes and Pihl [4] They found that ricin exerts its cytotoxic effect by enzymatic action on eukaryotic ribosomes resulting in inhibition of protein synthesis [3,4,5]. Ricin conjugated with specific antibodies, other proteins, peptides or nanoparticles can be selectively directed to target cells This ensures the possibility of a huge application of this toxin in medicine [40,41,42,43,44]. Crystal structure has been obtained from the PDB protein Both subunits are linked by a single disulfide bond.
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