From Proteopedia

Background on Ricin

Ricin is a toxin protein found in castor beans and the seeds of the castor oil plant. This heterodimeric protein is produced as a part of the waste that comes from the production of castor oil. Ricin was discovered more than a century ago when the protein was isolated from seeds by Stillmark. The protein is considered toxic due to its observed ability to clump up red blood cells. Later studies showed that ricin was a mixture of the potent cytotoxin and hemagglutinin. Such mechanism of the ricin was discovered on 28S ribosomal RNA. Since then, several functionally related proteins have been discovered from different plants. Such proteins are referred to as ribosome-inactivating proteins due to their ability to irreversibly inactivate eukaryotic ribosomes and terminating protein synthesis. Certain types of ricin known as ‘type I Ricins’ have toxic characteristics however it is seen that they do not have the capability to enter cells in order to reach the ribosomes. Other types are known as ‘type II Ricin’ however, have the capability to enter the cells due to their differences in structures.

Structure

Type I Ricin only consists of the A-chain whereas Type II Ricin is comprised of the A-chain and the B-chain which are folded peptide chains, with the two chains linked by disulfide bonds. Ricin has a molecular weight of 64-63 kDa, with the A-chain being 32 kDa and the B-chain being 36 kDa. The A-chain has the conformation of a globular protein domain with 267 amino acids consisting of 8 alpha-helices and 8 beta-sheets with the active site as a long cleft on its surface. The active site consists of a key catalytic residue Glutamic acid 177 which is deprotonated to glutamate reducing the activity immensely. Whereas the B-chain has the conformation of a barbell structure consisting of 26 amino acids, with a sugar-binding site at each end which allows it to hydrogen bond to galactose and N-acetyl galactosamine that is found on cell surfaces. The B-chain and the A-chain respectively do not cause the ricin to be toxic, Ricin’s toxicity is due to the presence of both chains because of their crucial roles together. The B-chain’s role is to acquire entry into eukaryotic cells, meanwhile, the A-chain is responsible for the toxicity because of its RNA N-glycosidase activity. Once the molecule enters the cell, the B-chain dissociates from the A-chain leaving it to exert its toxicity.