User:Robert Pearson/Sandbox 1

Function

Ricin is defined as a type 2 ribosome inactivating protein (RIP). Type 1 RIPs are made up of a single protein chain that demonstrate catalytic activity. Type 2 RIPs are made up of two protein chains which together will form a heterodimeric complex. Type 2 RIPs consist of an A chain that functions similarly to the type 1 RIP, bonded together by a disulfide bond and joining together a B chain. Although the B chain doesn’t demonstrate any catalytic activity, it does act in the transport of the AB chain from the cell surface. The AB chain is transported by vesicle carriers to the endoplasmic reticulum. Once the ribosome inactivating proteins have entered the body, both type 1 and type 2 RIPs are fully functional and destructive to the ribosomes. Although both RIP types are functional at this state, only type 2 will show cytotoxicity. This is because of the lectin properties that makeup the B chain. In order for the ribosome inactivating properties to be displayed, the ricin disulfide bond must be cleaved.

Disease

The Ricin A chain (RTA) is responsible for the cleavage of glycosidic bonds found in the large rRNA of the 60S subunit of the ribosome. RTA will irreversibly hydrolyze the N-glycosidic bond of the adenine residue, but not alter RNA’s phosphodiester backbone. The ricin targets A4324, a residue which is specific to all ribosomes found in eukaryotes. Depurination will then proceed rapidly and completely inactivate the ribosome, causing dangerous and toxic effects due to protein synthesis inhibition. As a single RTA molecule moves into the cytosol it is able to further depurinate and inhibit the function of approximately 1500 ribosomes per minute.

Relevance

Structural highlights