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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.

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The heterodimeric plant toxin ricin has been refined to 2.5 A resolution. The B-chain lectin (RTB) is described in detail. The protein has two major domains, each of which has a galactose binding site. RTB has no regular secondary structure but displays several omega loops. Each RTB domain is made of three copies of a primitive 40 residue folding unit, which pack around a pseudo threefold axis. In each domain, galactose binds in a shallow cleft formed by a three residue peptide kink on the bottom and an aromatic ring on the top. At the back of the cleft, an aspartate forms hydrogen bonds to the C3 and C4 hydroxyls of galactose, whereas a glutamine bonds to the C4 alcohol, helping to define specific epimer binding. In addition to analyzing the sugar binding mechanism, the assembly of subdomain units around the pseudo threefold axis of each domain is described. The subdomains contribute conserved Trp, Leu, and Ile residues to a compact central hydrophobic core. This tight threefold binding probably drives the peptide folding and stabilizes the protein structure.

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The plant cytotoxin ricin consists of two disulfide-linked chains, each of about 30,000 daltons. An initial model based on a 2.8 A MIR electron density map has been refined against 2.5 A data using rounds of hand rebuilding coupled with either a restrained least squares algorithm or molecular dynamics (XPLOR). The last model (9) has an R factor of 21.6% and RMS deviations from standard bond lengths and angles of 0.021 A and 4.67 degrees, respectively. Refinement required several peptide segments in the original model to be adjusted translationally along the electron density. A wide range of lesser changes were also made. The RMS deviation of backbone atoms between the original and model 9 was 1.89 A. Molecular dynamics proved to be a very powerful refinement tool. However, tests showed that it could not replace human intervention in making adjustments such as local translations of the peptide chain. The R factor is not a completely satisfactory indicator of refinement progress; difference Fouriers, when observed carefully, may be a better monitor.

Ricin is a dimeric toxin from the castor bean Ricinus communis, which is composed of a sugar-binding subunit (B) that attaches to receptors on the surfaces of target cells and a subunit (A) with enzymatic activity that attacks and inactivates ribosomes. We report here that comparison of amino-acid sequence data with high-resolution structure analysis of the ricin B subunit shows it to be the product of a series of gene duplications. The modern protein has two sugar-binding domains, each of which is composed of three copies of a more ancient galactose-binding peptide of about 40 residues.