In May 2013, President Barack Obama was sent a letter laced with the toxic extract of the castor bean. This toxin, ricin, is one of the most poisonous naturally occurring substances known, and can cause death in less than a day. Issues arises in how easily castor beans can be obtained and processed to produce a concentrated source of ricin. Ricin is a protein with two chains, an A chain and a B chain. The A chain is enzymic and causes the toxicity. The B chain is not toxic, but serves as a binding agent and aids the A chain in entering the cell. When a cell is infected with ricin, the B chain binds to receptors on the outside of the cell, causing the cell to take in the protein through endocytosis. The ricin protein is then transported to the endoplasmic reticulum where the A chain then translocates to the cytosol. The active site of the A chain only binds to a specific adenine molecule in the RNA of a ribosome. Once bound, the ricin irreversibly inactivates the ribosome, so the cell cannot produce proteins, eventually leading to cell death. Despite the dangerous implications of ricin, such use in terrorism and warfare, ricin can also be used to treat cancer. The toxic A chain of ricin may be attached to a binding protein that only targets cancer cells. This modified form of ricin, an immunotoxin, would then take effect on and kill cancer cells. A deep understanding of toxins and how they affect a cell can give a toxic killer the opportunity to be a life saver. With more research, immunotoxins may be the most efficient treatment to cancer up to date.

How Ricin

Works

One can be exposed to Ricin through three ways: inhalation, ingestion, or contact with skin and eyes. Among a fever and

coughing, symptoms of Ricin exposure include edemas, seizures, and kidney failure, and eventually result in death of the victim.

Works Cited1. Berkman, Frank. "Homeland Security: Silk Road Vendor Sent Obama Ricin Letter." Mashable. N.p., 18 Nov. 2013. Web. 01 May 2014.2. "Department of Animal Science - Plants Poisonous to Livestock." Cornell University Department of Animal Science. Cornell University,

6 Feb. 2014. Web. 01 May 2014.3. Endo, Y., and K. Tsurugi. "The RNA N-glycosidase Activity of Ricin A-chain. The Characteristics of the Enzymatic Activity of Ricin A-

chain with Ribosomes and with RRNA." Jbc.org. The Journal of Biological Chemistry, 25 June 1988. Web. 01 May 2014.4. "Facts About Ricin." CDC. N.p., 9 May 2013. Web. 01 May 2014.5. Goodsell, David. "Ricin." Protein Data Bank. RCSB, May 2013. Web. 01 May 2014.6. Jennifer, Audi, Belson Martin, Patel Manish, Schier Joshua, and Osterloh John. "Ricin Poisoning." JAMA Network. Journal of the

American Medical Association, 09 Nov. 2005. Web. 01 May 2014.7. Lord, J. M., L. M. Roberts, and J. D. Robertus. "Ricin: Structure, Mode of Action, and Some Current Applications." The FASEB

Journal. N.p., Feb. 1994. Web. 01 May 2014.Monfort, W., J. E. Villafranca, A. F. Monzingo, S. R. Ernst, B. Katzin, E. Rutenber, N.

8. H. Xuong, R. Hamlin, and J. D. Robertus. "The Three-dimensional Structure of Ricin at 2.8 A." Jbc.org. The Journal of Biological Chemistry, 15 Apr. 1987. Web. 01 May 2014.

9. Olsnes, Sjur, and Alexander Pihl. "Different Biological Properties of the Two Constituent Peptide Chains of Ricin a Toxic Protein Inhibiting Protein Synthesis." Biochemistry. ACS Publications, July 1973. Web. 01 May 2014.

10. "Ricin Cancer Therapy Tested." BBC News. BBC, 03 Nov. 2003. Web. 01 May 2014.11. "Ricin Fact Sheet ." Federation of American Scientists. N.p., n.d. Web. 07 May 2014.12. "Ricin Symptoms, Causes, Treatment - What Are the Signs and Symptoms of Ricin Exposure? - MedicineNet." MedicineNet. N.p., 9

May 2013. Web. 01 May 2014.13. Schmitt, Eric, and Thom Shanker. "Qaeda Trying to Harness Toxin For Bombs, U.S. Officials Fear." The New York Times. The New

York Times, 12 Aug. 2011. Web. 01 May 2014.14. Schnell, R., P. Borchmann, J. O. Staak, J. Schindler, V. Ghetie, E. S. Vitteta, and A. Engert. "Clinical Evaluation of Ricin A-chain

Immunotoxins in Patients with Hodgkin?s Lymphoma." Annals of Oncology. Oxford Journals, 2013. Web. 01 May 2014.15. Welsh, Jennifer. "RICIN: Here's What The Poison Sent To US Officials Can Do." Business Insider. Business Insider, Inc, 17 Apr. 2013.

Web. 01 May 2014.

Both the A and B chains of the ricin protein are included in this model. An important

amino acid in the A chain (shown in green) is serine #265. Serine 265 interacts with Alpha-D-Mannose and is primarily responsible for

triggering the death of the cell. The B chain (shown in tan) interacts with receptors on the cell membrane to gain entry for the A chain. Amino

acids involved in these reactions are aspartic acid #22 and #25, asparagine #46, lysine #240, glutamine #35, and tyrosine #125, all of which are shown in the model. The struts are not a part of the protein,

but are included in the model to provide structural support.

The Worst Part of Waking up is Ricin in your CupKelly Borgerding, Jack Craig, Malia Fraioli, Cole Gibbs, Margaret Lichtenfels, Marley Loomis, Rachel Pierce, Melissa Requist,

Jack Rosenthal, Rylan Russell, Logan Sankey, Harry Wilson, Cindy Gay

Ricin targets cells by lodging itself in the cell membrane. With the aid of the non-toxic B chain, which is the carrier for the toxic A chain, the A

chain is able to enter the cell through endocytosis. During this process, the B chain remains in the interstitial fluid outside of the cell. Once Ricin

arrives in the cytoplasm, the A chain targets and and deactivates ribosomes at a rate of 1500 ribosomes per minute. Ribosomes are the location of mRNA translation; thus, their deactivation prevents protein

synthesis, leading to the enevitable death of the cell. 6

11

Abstract

Molecular Story