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51  structures 412  species 0  interactions 1501  sequences 251  architectures

Family: RicinB_lectin_2 (PF14200)

Summary: Ricin-type beta-trefoil lectin domain-like

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This is the Wikipedia entry entitled "Ricin". More...

Ricin Edit Wikipedia article

Not to be confused with raisin.
Castor oil plant, fruits
Castor beans

Ricin (pron.: /ˈraɪsɪn/), from the castor oil plant Ricinus communis, is a highly toxic, naturally occurring protein. A dose as small as a few grains of salt can kill an adult human. The LD50 of ricin is around 22 micrograms per kilogram (1.78 mg for an average adult, around 1⁄228 of a standard aspirin tablet/0.4 g gross) in humans if exposure is from injection or inhalation.[1] Oral exposure to ricin is far less toxic and a lethal dose can be up to 20–30 milligrams per kilogram.

Contents

[edit] Toxicity

Ricin is poisonous if inhaled, injected, or ingested, acting as a toxin by the inhibition of protein synthesis. It is resistant, but not impervious, to digestion by peptidases. By ingestion, the pathology of ricin is largely restricted to the gastrointestinal tract where it may cause mucosal injuries; with appropriate treatment, most patients will make a full recovery.[2] Because the symptoms are caused by failure to make protein, they emerge only after a variable delay from a few hours to a full day after exposure. An antidote has been developed by the U.K. military, although it has not yet been tested on humans.[3][4] A vaccine has been developed by the U.S. military which has so far shown to be safe and effective when lab mice were injected with antibody-rich blood mixed with ricin, and has had some human testing.[5] Symptomatic and supportive treatment are available. Long term organ damage is likely in survivors. Ricin causes severe diarrhea and victims can die of shock. Death typically occurs within 3–5 days of the initial exposure.[6] Abrin is a similar toxin, found in the highly ornamental rosary pea.

Deaths from ingesting castor plant seeds are rare, partly because of their indigestible capsule, and because the body can, with difficulty, digest ricin.[7] The pulp from eight beans is considered dangerous to an adult.[8] A solution of saline and glucose has been used to treat ricin overdose.[9] Rauber and Heard have written that close examination of early 20th century case reports indicates that public and professional perceptions of ricin toxicity "do not accurately reflect the capabilities of modern medical management."[10]

[edit] Overdosage

Most acute poisoning episodes in humans are the result of oral ingestion of castor beans, 5-20 of which could prove fatal to an adult. Victims often manifest nausea, diarrhea, tachycardia, hypotension and seizures persisting for up to a week. Blood, plasma or urine ricin concentrations may be measured to confirm diagnosis.[11]

[edit] Biochemistry

Ricin is classified as a type 2 ribosome inactivating protein (RIP). Whereas Type 1 RIPs consist of a single enzymatic protein chain, Type 2 RIPs, also known as holotoxins, are heterodimeric glycoproteins. Type 2 RIPs consist of an A chain that is functionally equivalent to a Type 1 RIP, covalently connected by a single disulfide bond to a B chain that is catalytically inactive, but serves to mediate entry of the A-B protein complex into the cytosol. Both Type 1 and Type 2 RIPs are functionally active against ribosomes in vitro, however only Type 2 RIPs display cytoxicity due to the lectin properties of the B chain. In order to display its ribosome inactivating function, the ricin disulfide bond must be reductively cleaved.[12]

[edit] Structure

Ribosome inactivating protein (Ricin A chain)
Ricin structure.png
Ricin structure. The A chain is shown in blue and the B chain in orange.
Identifiers
Symbol RIP
Pfam PF00161
InterPro IPR001574
PROSITE PDOC00248
SCOP 1paf
SUPERFAMILY 1paf
Ricin-type beta-trefoil lectin domain (Ricin B chain)
Identifiers
Symbol
Pfam PF00652
Pfam clan CL0066
PROSITE IPR000772
SCOP 1abr
SUPERFAMILY 1abr
CAZy CBM13

The tertiary structure of ricin was shown to be a globular, glycosylated heterodimer of approximately 60-65 kDA.[7] Ricin toxin A chain and ricin toxin B chain are of similar molecular weight, approximately 32 kDA and 34 kDA respectively.

  • Ricin A chain (RTA) is an N-glycoside hydrolase composed of 267 amino acids.[13] It has three structural domains with approximately 50% of the polypeptide arranged into alpha-helices and beta-sheets.[14] The three domains form a pronounced cleft that is the active site of RTA.
  • Ricin B chain (RTB) is a lectin composed of 262 amino acids that is able to bind terminal galactose residues on cell surfaces.[15] RTB form a bilobal, barbell-like structure lacking alpha-helices or beta-sheets where individual lobes contain three subdomains. At least one of these three subdomains in each homologous lobe possesses a sugar-binding pocket that gives RTB its functional character.

Many plants such as barley have the A chain but not the B chain. People do not get sick from eating large amounts of such products, as ricin A is of extremely low toxicity as long as the B chain is not present.

[edit] Entry into the cytosol

The ability of ricin to enter the cytosol depends on hydrogen bonding interactions between RTB amino acid residues and complex carbohydrates on the surface of eukaryotic cells containing either terminal N-acetylgalactosamine or beta-1,4-linked galactose residues. Additionally, the mannose-type glycans of ricin are able to bind cells that express mannose receptors.[16] Experimentally, RTB has been shown to bind to the cell surface on the order of 106-108 ricin molecules per cell surface.[17]

The profuse binding of ricin to surface membranes allows internalization with all types of membrane invaginations. Experimental evidence points to ricin uptake in both clathrin-coated pits, as well as clathrin-independent pathways including caveolae and macropinocytosis.[18][19] Vesicles shuttle ricin to endosomes that are delivered to the Golgi apparatus. The active acidification of endosomes are thought to have little effect on the functional properties of ricin. Because ricin is stable over a wide pH range, degradation in endosomes or lysosomes offer little or no protection against ricin.[20] Ricin molecules are thought to follow retrograde transport via early endosomes, the trans-Golgi network, and the Golgi to enter the lumen of the endoplasmic reticulum (ER).[21]

For ricin to function cytotoxically, RTA must be reductively cleaved from RTB in order to release a steric block of the RTA active site. This process is catalysed by the protein PDI (protein disulphide isomerase) that resides in the lumen of the ER.[22] Free RTA in the ER lumen then partially unfolds and partially buries into the ER membrane, where it is thought to mimic a misfolded membrane-associated protein.[23] Roles for the ER chaperones GRP94 [24] and EDEM [25] have been proposed prior to the 'dislocation' of RTA from the ER lumen to the cytosol in a manner that utilizes components of the endoplasmic reticulum-associated protein degradation (ERAD) pathway. ERAD normally removes misfolded ER proteins to the cytosol for their destruction by cytosolic proteasomes. Dislocation of RTA requires ER membrane-integral E3 ubiquitin ligase complexes,[26] but RTA avoids the ubiquitination that usually occurs with ERAD substrates because of its low content of lysine residues, which are the usual attachment sites for ubiquitin.[27] Thus RTA avoids the usual fate of dislocated proteins (destruction that is mediated by targeting ubiquitinylated proteins to the cytosolic proteasomes). In the mammalian cell cytosol, RTA then undergoes triage by cytosolic molecular chaperones that results in its folding to a catalytic conformation [24] that de-purinates ribosomes, thus halting protein synthesis.

[edit] Ribosome inactivation

Study of the N-glycosidase activity of ricin was pioneered by Endo and Tsurugi[28] who showed that RTA cleaves a glycosidic bond within the large rRNA of the 60S subunit of eukaryotic ribosomes. They subsequently showed RTA specifically and irreversibly hydrolyses the N-glycosidic bond of the adenine residue at position 4324 (A4324) within the 28S rRNA, but leaves the phosphodiester backbone of the RNA intact.[29] The ricin targets A4324 that is contained in a highly conserved sequence of 12 nucleotides universally found in eukaryotic ribosomes. The sequence, 5’-AGUACGAGAGGA-3’, termed the sarcin-ricin loop, is important in binding elongation factors during protein synthesis.[30] The depurination event rapidly and completely inactivates the ribosome, resulting in toxicity from inhibited protein synthesis. A single RTA molecule in the cytosol is capable of depurinating approximately 1500 ribosomes per minute.

[edit] Depurination reaction

Within the active site of RTA, there exist several invariant amino acid residues involved in the depurination of ribosomal RNA.[20] Although the exact mechanism of the event is unknown, key amino acid residues identified include tyrosine at positions 80 and 123, glutamic acid at position 177, and arginine at position 180. In particular, Arg180 and Glu177 have been shown to be involved in the catalytic mechanism, and not substrate binding, with enzyme kinetic studies involving RTA mutants. The model proposed by Mozingo and Robertus,[31] based x-ray structures, is as follows:

  1. Sarcin-ricin loop substrate binds RTA active site with target adenine stacking against tyr80 and tyr123.
  2. Arg180 is positioned such that it can protonate N-3 of adenine and break the bond between N-9 of the adenine ring and C-1’ of the ribose.
  3. Bond cleavage results in an oxycarbonium ion on the ribose, stabilized by Glu177.
  4. N-3 protonation of adenine by Arg180 allows deprotonation of a nearby water molecule.
  5. Resulting hydroxyl attacks ribose carbonium ion.
  6. Depurination of adenine results in a neutral ribose on an intact phosphodiester RNA backbone.

[edit] Manufacture

Ricin is easily purified from castor oil manufacturing waste. The aqueous phase left over from the oil extraction process is called waste mash. It would contain about 5–10% ricin by weight, but heating during the oil extraction process denatures the protein, making the resultant seed cake safe for use as animal feed. From fresh seed, separation requires chromatographic techniques similar to other plant proteins.[citation needed]

[edit] Patented extraction process

A process for extracting ricin has been described in a patent.[32] The described extraction method is very similar to that used for the preparation of soy protein isolates.

The patent was removed from the United States Patent and Trademark Office (USPTO) database sometime in 2004.[33][34] Modern theories of protein chemistry cast doubt on the effectiveness of the methods disclosed in the patent.[35]

[edit] Potential medicinal use

Some researchers have speculated about using ricins in the treatment of cancer, as a so-called "magic bullet" to destroy targeted cells.[36] Because ricin is a protein, it can be genetically linked to a monoclonal antibody to target malignant cells recognized by the antibody. The major problem with ricin is that its native internalization sequences are distributed throughout the protein. If any of these native internalization sequences are present in a therapeutic, then the drug will be internalized by, and kill, untargeted epithelial cells as well as targeted cancer cells.

Some researchers hope that modifying ricin will sufficiently lessen the likelihood that the ricin component of these immunotoxins will cause the wrong cells to internalize it, while still retaining its cell-killing activity when it is internalized by the targeted cells. Generally, however, ricin has been superseded for medical purposes by more practical fragments of bacterial toxins, such as diphtheria toxin, which is used in denileukin diftitox, an FDA-approved treatment for leukemia and lymphoma. No approved therapeutics contain ricin.

A promising approach is also to use the non-toxic B subunit as a vehicle for delivering antigens into cells thus greatly increasing their immunogenicity. Use of ricin as an adjuvant has potential implications for developing mucosal vaccines.

Ricinine has some insecticidal effects on three insect pests as well as a hepatoprotective activity. Ricinine, when administered to mice at low doses has memory-improving effects. The signs of intoxication caused by ricinine can be used as chemical model of epilepsy in the screening of anticonvulsant drugs.[37]

[edit] Incidents involving ricin

Main article: Incidents involving ricin

Ricin has been involved in a number of incidents, including the high-profile assassination of Georgi Markov using a weapon disguised as an umbrella.

The ingestion of Ricinus communis cake is responsible for fatal ricin poisoning in animals.[38]

[edit] Use as a chemical or biological warfare agent

The United States investigated ricin for its military potential during World War I.[39] At that time it was being considered for use either as a toxic dust or as a coating for bullets and shrapnel. The dust cloud concept could not be adequately developed, and the coated bullet/shrapnel concept would violate the Hague Convention of 1899 (adopted in U.S. law at 32 Stat. 1903), specifically Annex § 2, Ch.1, Article 23, stating "...it is especially prohibited...[t]o employ poison or poisoned arms".[40] World War I ended before the U.S. weaponized ricin.

During WWII the US and Canada undertook studying ricin in cluster bombs.[41] Though there were plans for mass production and several field trials with different bomblet concepts, the end conclusion was that it was no more economical than using phosgene. This conclusion was based on comparison of the final weapons rather than ricin's toxicity (LCt50 ~40 mg·min/m3). Ricin was given the military symbol W or later WA. Interest in it continued for a short period after WWII, but soon subsided when the U.S. Army Chemical Corps began a program to weaponize sarin.

The Soviet Union also possessed weaponized ricin. There were speculations that the KGB used it outside of the Soviet bloc; however, this was never proven. In 1978, the Bulgarian dissident Georgi Markov was assassinated by Bulgarian secret police who surreptitiously 'shot' him on a London street with a modified umbrella using compressed gas to fire a tiny pellet contaminated with ricin into his leg.[2][42] He died in a hospital a few days later; his body was passed to a special poison branch of the British Ministry of Defence (MOD) that discovered the pellet during an autopsy. The prime suspects were the Bulgarian secret police: Georgi Markov had defected from Bulgaria some years previously and had subsequently written books and made radio broadcasts which were highly critical of the Bulgarian communist regime. However, it was believed at the time that Bulgaria would not have been able to produce the pellet, and it was also believed that the KGB had supplied it. The KGB denied any involvement although high-profile KGB defectors Oleg Kalugin and Oleg Gordievsky have since confirmed the KGB's involvement. Earlier, Soviet dissident Aleksandr Solzhenitsyn also suffered (but survived) ricin-like symptoms after a 1971 encounter with KGB agents.[43]

Despite ricin's extreme toxicity and utility as an agent of chemical/biological warfare, it is extremely difficult to limit the production of the toxin. The castor bean plant from which ricin is derived is a common ornamental and can be grown at home without any special care, and the major reason ricin is a public health threat is that it is easy to obtain.[citation needed]

Under both the 1972 Biological Weapons Convention and the 1997 Chemical Weapons Convention, ricin is listed as a schedule 1 controlled substance. Despite this, more than 1 million tonnes of castor beans are processed each year, and approximately 5% of the total is rendered into a waste containing negligible concentrations of undenatured ricin toxin.[44]

Ricin is several orders of magnitude less toxic than botulinum or tetanus toxin, but the latter are harder to come by. Compared to botulinum or anthrax as biological weapons or chemical weapons, the quantity of ricin required to achieve LD50 over a large geographic area is significantly more than an agent such as anthrax (tons of ricin vs. only kilogram quantities of anthrax).[45] Ricin is easy to produce, but is not as practical nor likely to cause as many casualties as other agents.[2] Ricin is inactivated (the protein changes structure and becomes less dangerous) much more readily than anthrax spores, which may remain lethal for decades. Jan van Aken, a Dutch expert on biological weapons, explained in a report for The Sunshine Project that Al Qaeda's experiments with ricin suggest their inability to produce botulinum or anthrax.[46]

Ian Davison, a British white supremacist and neo-Nazi, was arrested in 2009 for planning terrorist attacks involving ricin.

In 2011 the US government discovered information that terrorist groups were attempting to obtain large amounts of castor beans for weaponized ricin use.[47]

On November 1, 2011 the FBI arrested four North Georgia men and charged them in plots to purchase explosives, a silencer, and to manufacture the biological toxin ricin from castor beans.[48]

[edit] In popular culture

 This article may contain trivial, minor or unrelated references in popular culture. Please reorganize this content to explain the subject's impact on popular culture rather than simply listing appearances, and remove trivial references. (March 2013)
  • Ricin is a recurring plot device on the AMC drama series Breaking Bad.
  • Ricin was blamed for the poisoning of the main character, Adrian Monk, in episode 8.15 of the TV show Monk.
  • Ricin was the poison used to kill a chef, in the episode "Red herring" (season 2 episode 15) of the series "The Mentalist".
  • Ricin was used to murder a victim in the episode "Obsession" (season 7, episode 21) of the series "NCIS".
  • Santana mentions that she plans to "ricin [Sue Sylvester's] protein shakes" in the episode "Diva" (Season 4, Episode 13) of Glee.
  • Ricin was used in an explosive device planted inside of a cake at the United Nations in the episode "The Water is Wide" (Season 2, Episode 15) of The Unit.

[edit] References

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  3. ^ Rincon, Paul (2009-11-11). "http://news.bbc.co.uk/1/hi/sci/tech/8351666.stm". BBC News. Retrieved 2010-09-01. 
  4. ^ "Human trial proves ricin vaccine safe, induces neutralizing antibodies; further tests planned". University of Texas Southwestern Medical Center. 2006-01-30. Retrieved 2012-05-07. 
  5. ^ Karen Fleming-Michael (2005-09-01). "http://www.dcmilitary.com/dcmilitary_archives/stories/090105/36813-1.shtml". Dcmilitary.com. Retrieved 2010-09-01. 
  6. ^ "The Emergency Response Safety and Health Database: Biotoxin: RICIN". Centers for Disease Control and Prevention (CDC). 2008-08-01. Retrieved 2011-02-17. 
  7. ^ a b Aplin PJ, Eliseo T (1997). "Ingestion of castor oil plant seeds". Med. J. Aust. 167 (5): 260–1. PMID 9315014. 
  8. ^ Wedin GP, Neal JS, Everson GW, Krenzelok EP (1986). "Castor bean poisoning". American Journal of Emergency Medicine 4 (3): 259–61. doi:10.1016/0735-6757(86)90080-X. PMID 3964368. 
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  10. ^ Rauber A, Heard J (1985). "Castor bean toxicity re-examined: a new perspective". Veterinary and Human Toxicology 27 (6): 498–502. PMID 4082461. 
  11. ^ R. Baselt, Disposition of Toxic Drugs and Chemicals in Man, 8th edition, Biomedical Publications, Foster City, CA, 2008, pp. 1381-1383.
  12. ^ Wright HT, Robertus JD (1987). "The intersubunit disulfide bridge of ricin is essential for cytotoxicity". Arch Biochem Biophys 256 (1): 280–4. doi:10.1016/0003-9861(87)90447-4. PMID 3606124. 
  13. ^ Olnes S, Pihl A (1973). "Different biological properties of the two constituent peptide chains of ricin, a toxic protein inhibiting protein synthesis". Biochemistry 12 (16): 3121–26. doi:10.1021/bi00740a028. PMID 4730499. 
  14. ^ Weston SA, Tucker AD, Thatcher DR et al. (1994). "X-ray structure of recombinant ricin A-chain at 1.8 A resolution". J Mol Biol 244 (4): 410–22. doi:10.1006/jmbi.1994.1739. PMID 7990130. 
  15. ^ Wales R, Richardson PT, Robers LM, Woodland HR et al. (1991). "Mutational analysis of the galactose binding ability of recombinant ricin b chain". J Biol Chem 266: 19172–79. 
  16. ^ Magnusson AS, Kjeken R, Berg T (1993). "Characterization of two distinct pathways of endocytosis of ricin by rat liver endothelial cells". Exp Cell Res 205 (1): 118–25. doi:10.1006/excr.1993.1065. PMID 8453986. 
  17. ^ Sphyris N, Lord JM, Wales R et al. (1995). "Mutational analys is of the ricinus lectin b-chains: Galactose-binding ability of the gamma subdomain of ricinus communis agglutin b-chain". J Biol Chem 270 (35): 20292–97. doi:10.1074/jbc.270.35.20292. PMID 7657599. 
  18. ^ Moya M, Dautry-Varsat A, Goud B et al. (1985). "Inhibition of coated pit formation in Hep2 cells blocks the cytotoxicity of diphtheria toxin but not that of ricin toxin". J Cell Biol 101 (2): 548–59. doi:10.1083/jcb.101.2.548. PMC 2113662. PMID 2862151. 
  19. ^ Nichols, BJ, Lippincott-Schwartz J (2001). "Endocytosis without clathrin coats". Trends Cell Biol 11 (10): 406–12. doi:10.1016/S0962-8924(01)02107-9. PMID 11567873. 
  20. ^ a b Lord MJ, Jolliffe NA, Marsden CJ et al. (2003). "Ricin Mechanisms of Cytotoxicity". Toxicol Rev 22 (1): 53–64. doi:10.2165/00139709-200322010-00006. PMID 14579547. 
  21. ^ Spooner, RA; DC Smith, AJ Easton, LM Roberts, JM Lord (2006). "Retrograde transport pathways utilised by viruses and protein toxins". Virology Journal 3: 26–35. doi:10.1186/1743-422X-3-26. PMC 1524934. PMID 16603059. 
  22. ^ Spooner, RA; Peter D. WATSON, Catherine J. MARSDEN, Daniel C. SMITH, Katherine A. H. MOORE, Jonathon P. COOK, J. Michael LORD and Lynne M. ROBERTS (2004). "Protein disulphide-isomerase reduces ricin to its A and B chains in the endoplasmic reticulum". Biochem. J. 383 (Pt 2): 285–293. doi:10.1042/BJ20040742. PMC 1134069. PMID 15225124. 
  23. ^ Mayerhofer, P.U.; Cook, J. P., Wahlman, J., Pinheiro, T. T. J., Moore, K. A. H., Lord, J. M., Johnson, A. E. and Roberts, L. M. (2009). "A chain insertion into endoplasmic reticulum membranes is triggered by a temperature increase to 37(degrees)C". Journal of Biological Chemistry 284 (15): 10232–10242. doi:10.1074/jbc.M808387200. PMC 2665077. PMID 19211561. 
  24. ^ a b Spooner, RA; Hart, Philip J. and Cook, Jonathan P. and Pietroni, Paola and Rogon, Christian and Höhfeld, Jörg and Roberts, Lynne M. and Lord, J. Mike (2008). "Cytosolic chaperones influence the fate of a toxin dislocated from the endoplasmic reticulum". Proceedings of the National Academy of Sciences 105 (45): 17408–17413. doi:10.1073/pnas.0809013105. 
  25. ^ Slominska-Wojewodzka, Monika; Tone F. Gregers, Sébastien Wälchli, and Kirsten Sandvig (2006). "EDEM Is Involved in Retrotranslocation of Ricin from the Endoplasmic Reticulum to the Cytosol". Mol Biol Cell 17 (4): 1664–1675. doi:10.1091/mbc.E05-10-0961. PMC 1415288. PMID 16452630. 
  26. ^ Li, S; Spooner, R. A., Allen, S. C. H., Guise, C. P., Ladds, G., Schnoeder, T., Schmitt, M. J., Lord, J. M., and Roberts, L. M. (2010). "Folding-competent and folding-defective forms of ricin A chain have different fates after retrotranslocation from the endoplasmic reticulum". Molecular Biology of the Cell 21 (15): 2543–2554. doi:10.1091/mbc.E09-08-0743. PMC 2912342. PMID 20519439. 
  27. ^ Deeks ED, Cook JP, Day PJ et al. (2002). "The low lysine content of ricin A chain reduces the risk of proteolytic degradation after translocation from the endoplasmic reticulum to the cytosol". Biochemistry 41 (10): 3405–13. doi:10.1021/bi011580v. PMID 11876649. 
  28. ^ Endo Y, Tsurugi K (1987). "RNA N-glycosidase activity of ricin A-chain: mechanism of action of the toxic lectin ricin on eukaryotic ribosomes". J Biol Chem 262 (17): 8128–30. PMID 3036799. 
  29. ^ Endo Y, Tsurugi K (1998). "The RNA N-glycosidase activity of ricin A chain". J Biol Chem 263 (18): 8735–9. PMID 3288622. 
  30. ^ Sperti S, Montanaro L, Mattioli A et al. (1973). "Inhibition by ricin of protein synthesis in vitro: 60 S ribosomal subunit as the target of the toxin". Biochem J 136 (3): 813–5. PMC 1166019. PMID 4360718. 
  31. ^ Monzingo AF, Robertus JD (1992). "X-ray analysis of substrate analogs in the ricin A-chain active site". J Mol Biol 244 (4): 410–22. doi:10.1006/jmbi.1994.1739. PMID 7990130. 
  32. ^ "Preparation of Toxic Ricin", U.S. Patent 3,060,165, assigned to the U.S. Secretary of the Army, inventors: Harry L. Craig, O.H. Alderks, Alsoph H. Corwin, Sally H. Dieke, and Charlotte Karel (granted October 23, 1962)
  33. ^ "Harry L. Craig, O.H. Alderks, Alsoph H. Corwin, Sally H. Dieke, and Charlotte Karel, US Patent 3,060,165, "Preparation of Toxic Ricin", granted October 23, 1962". V3.espacenet.com. Retrieved 2010-09-01. 
  34. ^ "Ricin Patent". Cryptome.org. 2004-03-12. Retrieved 2010-09-01. 
  35. ^ John Pike. "http://www.globalsecurity.org/org/nsn/nsn-040723.htm". Globalsecurity.org. Retrieved 2010-09-01. 
  36. ^ Lord MJ, Jolliffe NA, Marsden CJ et al. (2003). "Ricin. Mechanisms of cytotoxicity". Toxicological Reviews 22 (1): 53–64. doi:10.2165/00139709-200322010-00006. PMID 14579547. 
  37. ^ Liu X., Li D."Biological activity of ricinine and outlook of its applied development" Chinese Journal of Pharmacology and Toxicology 2006 20:1 (76-78)
  38. ^ Soto-Blanco B, Sinhorini IL, Gorniak SL, Schumaher-Henrique B (June 2002). "Ricinus communis cake poisoning in a dog". Vet Hum Toxicol 44 (3): 155–6. PMID 12046967. 
  39. ^ Augerson, William S.; Spektor, Dalia M.; United States Dept. of Defense, Office of the Secretary of Defense, National Defense Research Institute (U.S.) (2000). A Review of the Scientific Literature as it Pertains to Gulf War Illnesses. Rand Corporation, ISBN 978-0-8330-2680-4
  40. ^ "The Avalon Project â€” Laws of War : Laws and Customs of War on Land (Hague II); July 29, 1899". Avalon.law.yale.edu. Retrieved 2010-09-01. 
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  42. ^ "Ricin and the umbrella murder". CNN. January 7, 2003. Retrieved 2008-03-15. 
  43. ^ D. M. Thomas, Alexander Solzhenitsyn: A Century in His Life, 368–378
  44. ^ "Cornell University Department of Animal Science". Ansci.cornell.edu. Retrieved 2012-05-07. 
  45. ^ Kortepeter M.G., Parker G.W. (1999). Potential biological weapons threats 5 (4). U.S. Army Medical Research Institute of Infectious Diseases. pp. 523–527. 
  46. ^ van Aken, Jan (2001). "Biological Weapons: Research Projects of the German Army". Backgrounder Series #7. The Sunshine Project. 
  47. ^ Eric Schmitt and Thom Shanker (2011-08-13). "Al Qaeda trying to harness toxin for bombs, U.S. officials fear". The New York Times. Retrieved August 10, 2011. 
  48. ^ "North Georgia Men Arrested, Charged in Plots to Purchase Explosives, Silencer and to Manufacture a Biological Toxin". fbi.gov. 

[edit] External links

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This tab holds the annotation information that is stored in the Pfam database. As we move to using Wikipedia as our main source of annotation, the contents of this tab will be gradually replaced by the Wikipedia tab.

Ricin-type beta-trefoil lectin domain-like Provide feedback

No Pfam abstract.

Internal database links

Similarity to PfamA using HHSearch: Ricin_B_lectin Ricin_B_lectin CDtoxinA Botulinum_HA-17

External database links

PANDIT: PF14200
Pseudofam: PF14200
SYSTERS: RicinB_lectin_2

This tab holds annotation information from the InterPro database.

InterPro entry IPR000772

Ricin is a legume lectin from the seeds of the castor bean plant, Ricinus communis. The seeds are poisonous to people, animals and insects and just one milligram of ricin can kill an adult.

Primary structure analysis has shown the presence of a similar domain in many carbohydrate-recognition proteins like plant and bacterial AB-toxins, glycosidases or proteases [PUBMED:9603958, PUBMED:7664090, PUBMED:8844840]. This domain, known as the ricin B lectin domain, can be present in one or more copies and has been shown in some instance to bind simple sugars, such as galactose or lactose.

The ricin B lectin domain is composed of three homologous subdomains of 40 amino acids (alpha, beta and gamma) and a linker peptide of around 15 residues (lambda). It has been proposed that the ricin B lectin domain arose by gene triplication from a primitive 40 residue galactoside-binding peptide [PUBMED:3561502, PUBMED:1881882]. The most characteristic, though not completely conserved, sequence feature is the presence of a Q-W pattern. Consequently, the ricin B lectin domain as also been refered as the (QxW)3 domain and the three homologous regions as the QxW repeats [PUBMED:7664090, PUBMED:8844840]. A disulphide bond is also conserved in some of the QxW repeats [PUBMED:7664090].

The 3D structure of the ricin B chain has shown that the three QxW repeats pack around a pseudo threefold axis that is stabilised by the lambda linker [PUBMED:3561502]. The ricin B lectin domain has no major segments of a helix or beta sheet but each of the QxW repeats contains an omega loop [PUBMED:1881882]. An idealized omega-loop is a compact, contiguous segment of polypeptide that traces a 'loop-shaped' path in three-dimensional space; the main chain resembles a Greek omega.

Domain organisation

Below is a listing of the unique domain organisations or architectures in which this domain is found. More...

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Pfam Clan

This family is a member of clan Trefoil (CL0066), which contains the following 15 members:

AbfB Agglutinin Botulinum_HA-17 CDtoxinA DUF569 Fascin FGF FRG1 IL1 Ins145_P3_rec Kunitz_legume MIR Ricin_B_lectin RicinB_lectin_2 Toxin_R_bind_C

Alignments

We store a range of different sequence alignments for families. As well as the seed alignment from which the family is built, we provide the full alignment, generated by searching the sequence database using the family HMM. We also generate alignments using four representative proteomes (RP) sets, the NCBI sequence database, and our metagenomics sequence database. More...

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We make a range of alignments for each Pfam-A family. You can see a description of each above. You can view these alignments in various ways but please note that some types of alignment are never generated while others may not be available for all families, most commonly because the alignments are too large to handle.

  Seed
(49)		 Full
(1501)		 Representative proteomes NCBI
(2662)		 Meta
(47)
RP15
(285)		 RP35
(489)		 RP55
(608)		 RP75
(644)
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1Cannot generate PP/Heatmap alignments for seeds; no PP data available

Key: ✓ available, x not generated, — not available.

Format an alignment

  Seed
(49)		 Full
(1501)		 Representative proteomes NCBI
(2662)		 Meta
(47)
RP15
(285)		 RP35
(489)		 RP55
(608)		 RP75
(644)
Alignment:
Format:
Order:
Sequence:
Gaps:
Download/view:

Download options

We make all of our alignments available in Stockholm format. You can download them here as raw, plain text files or as gzip-compressed files.

  Seed
(49)		 Full
(1501)		 Representative proteomes NCBI
(2662)		 Meta
(47)
RP15
(285)		 RP35
(489)		 RP55
(608)		 RP75
(644)
Raw Stockholm Download   Download   Download   Download   Download   Download   Download   Download  
Gzipped Download   Download   Download   Download   Download   Download   Download   Download  

You can also download a FASTA format file containing the full-length sequences for all sequences in the full alignment.

External links

MyHits provides a collection of tools to handle multiple sequence alignments. For example, one can refine a seed alignment (sequence addition or removal, re-alignment or manual edition) and then search databases for remote homologs using HMMER3.

Pfam alignments:

HMM logo

HMM logos is one way of visualising profile HMMs. Logos provide a quick overview of the properties of an HMM in a graphical form. You can see a more detailed description of HMM logos and find out how you can interpret them here. More...

Trees

This page displays the phylogenetic tree for this family's seed alignment. We use FastTree to calculate neighbour join trees with a local bootstrap based on 100 resamples (shown next to the tree nodes). FastTree calculates approximately-maximum-likelihood phylogenetic trees from our seed alignment.

Note: You can also download the data file for the tree.

Curation and family details

This section shows the detailed information about the Pfam family. You can see the definitions of many of the terms in this section in the glossary and a fuller explanation of the scoring system that we use in the scores section of the help pages.

Curation View help on the curation process

Seed source: Jackhmmer:Q8X123
Previous IDs: none
Type: Domain
Author: Coggill P
Number in seed: 49
Number in full: 1501
Average length of the domain: 100.70 aa
Average identity of full alignment: 22 %
Average coverage of the sequence by the domain: 25.03 %

HMM information View help on HMM parameters

HMM build commands:
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 23193494 -E 1000 --cpu 4 HMM pfamseq
Model details:
Parameter Sequence Domain
Gathering cut-off 35.1 35.1
Trusted cut-off 35.1 35.1
Noise cut-off 35.0 35.0
Model length: 105
Family (HMM) version: 1
Download: download the raw HMM for this family

Species distribution

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This visualisation provides a simple graphical representation of the distribution of this family across species. You can find the original interactive tree in the adjacent tab. More...

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Structures

For those sequences which have a structure in the Protein DataBank, we use the mapping between UniProt, PDB and Pfam coordinate systems from the PDBe group, to allow us to map Pfam domains onto UniProt sequences and three-dimensional protein structures. The table below shows the structures on which the RicinB_lectin_2 domain has been found. There are 51 instances of this domain found in the PDB. Note that there may be multiple copies of the domain in a single PDB structure, since many structures contain multiple copies of the same protein seqence.

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