Ricin is a water-soluble glycoprotein from the seeds of the castor bean plant, Ricinus communis. This naturally occurring substance is one of the most poisonous toxins known. Its lethality is a direct result of its molecular architecture, which allows it to enter animal cells and disrupt cellular life.
The Two-Chain Composition
Ricin’s structure is a heterodimer, a protein composed of two distinct polypeptide chains: Ricin Toxin A (RTA) and Ricin Toxin B (RTB). The A-chain consists of 267 amino acids and the B-chain has 262, giving them similar molecular weights of approximately 32 kDa and 34 kDa. This two-part structure classifies ricin as a type 2 ribosome-inactivating protein (RIP).
The two chains are connected by a disulfide bond to form a single, functional unit. This composition of two different chains, one for binding and one for enzymatic activity, is a feature shared by other toxins.
Functional Roles of Each Chain
Each of ricin’s two chains performs a distinct job. The B-chain (RTB) functions as the targeting system, allowing the toxin to attach to a cell’s surface. RTB is a lectin, a protein that binds to specific sugar molecules like the galactose residues common on eukaryotic cells.
Once the B-chain has anchored the toxin, the A-chain (RTA) is poised to perform its function. The A-chain is the active, enzymatic component of the toxin and is an N-glycoside hydrolase, an enzyme that can cleave a specific type of chemical bond.
Mechanism of Cellular Entry and Toxicity
The toxic process begins when the ricin B-chain binds to galactose-containing molecules on a cell’s outer membrane. This attachment can be prolific, as between 10 to 100 million ricin molecules can bind to a single cell. This binding signals the cell to engulf the entire ricin molecule through endocytosis.
The internalized ricin travels through the cell’s transport system, moving through endosomes and the Golgi apparatus before reaching the endoplasmic reticulum (ER). Inside the ER, cellular enzymes cleave the disulfide bond that links the A and B chains. This step frees the RTA chain from the RTB chain.
Once liberated, the RTA chain moves from the ER into the cytosol, where it finds its targets: the ribosomes responsible for building the cell’s proteins. RTA is efficient and specific, targeting a sequence of ribosomal RNA within the large 60S ribosomal subunit. It acts as an enzyme to permanently remove a single adenine base (A4324) from a region known as the sarcin-ricin loop.
This single cut inactivates the ribosome, halting its ability to synthesize proteins. Without the continuous production of new proteins, cellular processes stop, and the cell quickly dies. The potency of ricin is explained by the catalytic nature of the A-chain, as a single RTA molecule can inactivate 1,500 to 2,000 ribosomes per minute.