To inhibit protein synthesis and induce cell death, plant ricin toxin and bacterial Shiga toxins enter the cell through the endocytic and retrograde secretory pathways. Stechmann et al. (2010) now identify two small-molecule inhibitors that selectively block endosome-to-Golgi retrieval of ricin and Shiga toxins and protect mice from ricin's deadly effects.

Ricin is a cytotoxic plant protein that inactivates ribosomes by hydrolyzing the N-glycosidic bond at position A4324 in eukaryotic 28S rRNA. Recent studies showed that a four-nucleotide loop, GAGA, can function as a minimum substrate for ricin (the first adenosine corresponds to the site of depurination). We previously clarified the solution structure of this loop by NMR spectroscopy [Orita et ...

The toxic subunit of ricin has been conjugated by a disulfide bound to a monoclonal murine antibody (J-5) specific for the common acute lymphoblastic leukemia antigen (CALLA) expressed on human lymphoblastic cells. Both the monoclonal antibody and ricin A chain retained their original biological activity after conjugation. The ricin A chain portion of this conjugate effectively inhibited protei...

We have found that cerulenin, an antibiotic that inhibits de novo fatty acid and cholesterol biosynthesis and fatty acylation of proteins, strongly inhibited the cytotoxicity of ricin, modeccin, Pseudomonas toxin, and diphtheria toxin in a brefeldin A (BFA)-resistant mutant of Vero cells (BER-40). The protective effect of cerulenin against ricin was also observed in two other BFA-resistant cell...

Introduction: We have formerly developed a point-of-care Immunochromatographic Test (ICT) for the diagnosis of ricin pulmonary intoxication, which was intended to be utilised after nasal swabbing. The requested limit of sensitivity for such a diagnosis was calculated but not tested experimentally, and no other sample source was considered. Here, this approach was evaluated on various samples ta...

The flotillin proteins are localized in lipid domains at the plasma membrane as well as in intracellular compartments. In the present study, we examined the importance of flotillin-1 and flotillin-2 for the uptake and transport of the bacterial Shiga toxin (Stx) and the plant toxin ricin and we investigated whether toxin binding and uptake were associated with flotillin relocalization. We obser...

Ricin toxin, an A-B toxin from Ricinus communis, induces cell death through the inhibition of protein synthesis. The toxin binds to the cell surface via its B chain (RTB) followed by its retrograde trafficking through intracellular compartments to the ER where the A chain (RTA) is transported across the membrane and into the cytosol. Ricin A chain is transported across the ER membrane utilizing...

Ricin is a potent glycoprotein toxin that is structurally composed of two subunits joined via a disulfide bond: a ~30 kDa subunit A (RTA) and a ~32 kDa subunit B (RTB). There are fears of ricin being used as a weapon for warfare and terrorism and, as such, there is an increasing need for the development of immunodiagnostic reagents targeted towards this toxin. This article describes the product...

Ricin is a type II ribosome-inactivating protein (RIP) that depurinates A4324 at the sarcin-ricin loop of 28 S ribosomal RNA (rRNA), thus inactivating the ribosome by preventing elongation factors from binding to the GTPase activation centre. Recent studies have disclosed that the conserved C-terminal domain (CTD) of eukaryotic ribosomal P stalk proteins is involved in the process that RIPs tar...