Ricin (Ribosomes are important)

Lots of chatter in the news today about finding ricin in a Vegas hotel room.


Image of PDB ID 2AAI from Wikipedia

Ricin works by inhibiting protein synthesis at the ribosomal level. This is a well-known method of killing something, and one on which many antibiotics work.

You'll note this looks different than most of my structures, and that's because ricin is a giant molecule in comparison - about 100 times larger than most of what you see here. It's a protein.

Proteins tend to be fragile things. Small molecules are a lot like jellybeans to proteins' gingerbread houses. Knock a jellybean off the table (or eat a small molecule), and it'll hold up pretty well. Knock a gingerbread house off the table (or eat a protein), and it'll end up in pieces. For this reason, you typically have to bypass the wrecking ball of the gut and inject proteins - or maybe inhale them - we only worked out this trick effectively with perhaps the best known protein hormone, insulin, recently.

For whatever reason ricin is apparently different, and is toxic orally. Curious to hear from anyone who knows why it's so sturdy - usually your body digests protein toxins like any other protein (i.e., meat).


More like this

Isn't insulin a big peptide -- or a very small protein ?

The curious thing about digestion is that the acid in your stomach doesn't really break up proteins. Rather, it creates an excellent operating pH for pepsin, and denatures proteins to give pepsin access. In general, proteases such as pepsin cannot bind to or digest energetically stable folded structures. The B chain of ricin (orange) is very rich with disulfide bonds, which will likely help it retain a rigid structure under acidic conditions and thus inhibit the action of pepsin. Charge characteristics of the structure might also make it resistant to denaturation.

You forgot to mention why ricin is such a deadly poison, though. Inhibitors like erythromycin work by binding to the ribosome and getting in the way of activity, so 1 molecule of erythromycin can only inhibit 1 ribosome. Ricin, however, is an enzyme that can chemically modify a ribosome. Because of this, a single molecule of ricin is sufficient to kill an entire cell's worth of ribosomes.

Not sure why it is toxic orally, but that structure is kind of odd. The orangeish chain has no secondary structure elements at all. I'm sort of surprised they were able to get density for all of that. Looks like I'll have to read the paper.

This is from my memory so somebody can help me if I mention something wrong. Ricin actually occurs in many natural substances that we eat every day. However, only the ricin from the castor bean has the necessary subunit for cellular uptake,this subunit may be represented above as the blue or orange structure.

Hermit, you are correct. The blue subunit above is catalytic and rather common. The orange domain to which it is fused, however, is the unique feature of the molecule in castor beans, and what allows it to enter our cells.

@skw - The differences between the A & B Chains here are just due to the way that the pdb file was modeled. It looks like chain A was rendered as a ribbon, and chain B was rendered as a loop. No difference in the density.