Ricin: structure, mode of action, and some current applications

Abstract

Ricin is an abundant protein component of Ricinus communis seeds (castor beans) that is exquisitely toxic to mammalian cells. It consists of an enzymic polypeptide that catalyzes the N-glycosidic cleavage of a specific adenine residue from 28S ribosomal RNA, joined by a single disulfide bond to a galactose (cell)-binding lectin. The enzymatic activity renders ribosomes containing depurinated 28S RNA incapable of protein synthesis. The bipartite molecular structure of ricin allows it to bind to the mammalian cell surface, enter via endocytic uptake, and deliver the catalytically active polypeptide into the cell cytosol where it irreversibly inhibits protein synthesis causing cell death. Because of its cytotoxic potency, modified ricin is being used for the selective killing of unwanted cells and for the toxigenic ablation of cell lineages in transgenic organisms.

Spontaneous poisoning by Ricinus communis (Euphorbiaceae) in cattle

“…Ricin is the main alkaloid involved in the pathogenesis of poisoning because this toxin is 100-2000 times more toxic than agglutinin (Lin et al 1980, Lord et al 1994, Brandt et al 2001. These toxins bind to their receptors on cell membranes, are internalized and are transported by endocytosis to the endoplasmic reticulum where they cause protein inactivation and cell death.…”

“…In the cardiovascular system, ricin causes a severe reduction in the intracellular calcium flux (Ma et al 1995). These changes are largely responsible for the bleeding observed in the various tissues of cattle that died of intoxication (Lord et al 1994, Christiansen et al 1991, Spooner & Watson 2010. R. communis is often cited by farmers as the cause of death, especially of cattle, in epidemiological surveys conducted by our team in semiarid regions of Pernambuco and Paraíba.…”

Effects of ricin extracted from seeds of the castor bean (ricinuscommunis) on cytotoxicity and tumorigenesis of melanoma cells

“…Ricin consists of two polypeptide chains (A chain: 30 kDa and B chain: 34 kDa), which link with each other via disulfide bridges (-S-S-) (Funatsu et al, 1976), and the molecular weight of ricin is about 64 kDa Ricin is one of the most poisonous substances in nature and highly toxic in humans and animals (Funatsu et al, 1976;Lord et al, 1994). When this toxic protein enters a cell, particularly via inhalation or ingestion, it blocks the ability of cells to synthesize its own proteins, leading to cellular and organ damage.…”

“…Due to its toxicity, ricin can be used for bioterrorism. Ricin can bind with high affinity to galactose residues on the cell surface and is transported through the cell membranes to cause cell death (Funatsu et al, 1976;Kumar et al, 2004;Lord et al, 1994).Although both chains contribute to toxicity, the A chain is associated with higher poisonous property and has been more studied. The A chain of ricin has been reported to be a strong immunotoxin for cells (Engert et al, 1994;Engert et al, 1990;Weidle et al, 2014).…”

Influência da concentração de NaCl e pH na extração de ricina em torta de mamona (Ricinus communis L.) e sua caracterização por eletroforese

“…Esta proteína pertence à família das proteínas inibidoras de ribossomo (RIPs) do tipo II (OLSNES, 2004;LORD et al, 1994;. MONZINGO et al, 1993).…”