MadSci Network: Biochemistry

Re: What makes ricin such a potent poison ?

Area: Biochemistry
Posted By: Michael Onken, WashU
Date: Mon Feb 24 17:37:49 1997
Message ID: 853824170.Bc

Ricin is a protein produced by the castor oil plant, Ricinus communis, which is highly toxic (the minimal lethal dose is around 1 g / kg body weight, that means 1/15th of a milligram could kill a 150 lb. person). Ricin can be a dangerous contaminant, making the production of castor oil a precisely controled process.

Ricin is a type II RIP (ribosome inactivating protein) which consists of two smaller proteins held together covalently by a disulfide bridge. These two proteins are the A chain (RTA) and the B chain (RTB). To understand the toxicity of ricin, we need to look at the activities of these two subunits.

RTA is an N-glycosidase, which removes the bases from nucleic acids like DNA or RNA. RTA specifically targets a sequence in ribosomal RNA (the GAGA tetraloop of 18S rRNA) which completely inactivates the ribosomes, which are the machinery for producing proteins in the cell. Without functional ribosomes, the cell cannot produce the enzymes it needs to operate and dies. On its own, RTA cannot enter the cell to get access to the ribosomes, so it only inactivates ribosomes in the laboratory, which has classified it a type I RIP (which is non-toxic).

RTB is a lectin (a protein which binds to sugar) which is specific for sugars containing galactose (which is a component of lactose - the sugar in milk). Since most proteins on the outsides of cells are decorated by complex sugar chains, several of which contain galactose, there are lots of places for RTB to stick to the outsides of cells. Beside sticking to the outside, RTB can piggyback on these proteins as they are internalized into the cell (via the TGN), being carried into the cell itself.

So by attaching RTA to RTB, castor oil plants have created a ribosome inactivator that can be carried into the cell where it is toxic. This is the same strategy used by several other toxins: like Choleratoxin (which causes Cholera), Pertussistoxin (which causes Whopping Cough), Diptheriatoxin (which causes Diptheria), and others. In each case, a normally benign toxin is linked to a protein which gives it a way into the cell, where it is deadly.

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