Skip to main content

Ricin: structure, synthesis, and mode of action

  • Chapter
  • First Online:

Part of the book series: Topics in Current Genetics ((TCG,volume 11))

Abstract

Ricin is a lectin produced by the seeds of the Ricinus communis plant. It is potently toxic to mammalian cells, where it acts to inhibit the essential process of protein synthesis. Structurally, ricin is a heterodimer comprised of an enzymatic polypeptide (the A chain) disulphide bonded to a cell-binding lectin (the B chain). After surface binding, the holotoxin is internalised to endosomes from where a small fraction can be transported by a retrograde route to the endoplasmic reticulum (ER). After reduction in the ER lumen, the A chain is rendered competent for translocation to the cytosol and, whilst most is apparently degraded there, a proportion evades degradation to refold and inactivate ribosomes. In this review we present our current understanding of the biosynthesis and mode of action of this highly cytotoxic plant protein.

This is a preview of subscription content, log in via an institution.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  • 1. Argent RH, Parrott AM, Day PJ, Roberts LM, Stockley PG, Lord JM, Radford SE (2000) Ribosome-mediated folding of partially unfolded ricin A-chain. J Biol Chem 275:9263-9269

    Article  CAS  PubMed  Google Scholar 

  • 2. Barbieri L, Valbonesi P, Bonora E, Gorini P, Bolognesi A, Stirpe F (1997) Polynucleotide:adenosine glycosidase activity of ribosome-inactivating proteins: effect on DNA, RNA and poly(A). Nucleic Acids Res 25:518-522

    Article  CAS  PubMed  Google Scholar 

  • 3. Beaumelle B, Taupiac MP, Lord JM, Roberts LM (1997) Ricin A chain can transport unfolded dihydrofolate reductase into the cytosol. J Biol Chem 272:22097-22102

    Article  CAS  PubMed  Google Scholar 

  • 4. Bellisola G, Fracasso G, Ippoliti R, Menestrina G, Rosen A, Solda S, Udali S, Tomazzolli R, Tridente G, Colombatti M (2004) Reductive activation of ricin and ricin A-chain immunotoxins by protein disulfide isomerase and thioredoxin reductase. Biochem Pharmacol 67:1721-1731

    Article  CAS  PubMed  Google Scholar 

  • 5. Brigotti M, Alfieri R, Sestili P, Bonelli M, Petronini PG, Guidarelli A, Barbieri L, Stirpe F, Sperti S (2002) Damage to nuclear DNA induced by Shiga toxin 1 and ricin in human endothelial cells. FASEB J 16:365-372

    Article  CAS  PubMed  Google Scholar 

  • 6. Butterworth AG, Lord JM (1983) Ricin and Ricinus communis agglutinin subunits are all derived from a single-size polypeptide precursor. Eur J Biochem 137:57-65

    CAS  PubMed  Google Scholar 

  • 7. Cawley DB, Hedbolm ML, Hoffman EJ, Houston LL (1977) Differential sensitivity of rat liver and wheat germ ribosomes to inhibition of polyuridylic acid translation by ricin A chain. Arch Biochem Biophys 182:690-695

    CAS  PubMed  Google Scholar 

  • 8. Chen A, Hu T, Mikoryak C, Draper RK (2002) Retrograde transport of protein toxins under conditions of COP1 disfunction. Biochim Biophys Acta 1589:124-139

    Article  CAS  PubMed  Google Scholar 

  • 9. Cosson P, Letourner F (1997) Coatomer (COP1)-coated vesicles: role in intracellular transport and protein sorting. Curr Opin Cell Biol 7:484-487

    Article  Google Scholar 

  • 10. Cosson P, Letourneur F (1994) Coatomer interaction with di-lysine endoplasmic reticulum retention motifs. Science 263:1629-1631

    CAS  PubMed  Google Scholar 

  • 11. Damke H, Baba T, van der Bliek AM, Schmid SL (1995) Clathrin-independent pinocytosis is induced in cells overexpressing a temperature-sensitive mutant of dynamin. J Cell Biol 131:69-80

    Article  CAS  PubMed  Google Scholar 

  • 12. Day PJ, Owens SR, Wesche J, Olsnes S, Roberts LM, Lord JM (2001) An interaction between ricin and calreticulin that may have implications for toxin trafficking. J Biol Chem 276:7202-7208

    Article  CAS  PubMed  Google Scholar 

  • 13. Day PJ, Pinheiro TJ, Roberts LM, Lord JM (2002) Binding of ricin A-chain to negatively charged phospholipid vesicles leads to protein structural changes and destabilizes the lipid bilayer. Biochemistry 41:2836-2843

    Article  CAS  PubMed  Google Scholar 

  • 14. Deeks ED, Cook JP, Day PJ, Smith DC, Roberts LM, Lord JM (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 41:3405-3413

    Article  CAS  PubMed  Google Scholar 

  • 15. Di Cola A, Frigerio L, Lord JM, Ceriotti A, Roberts LM (2001) Ricin A chain without its partner B chain is degraded after retrotranslocation from the endoplasmic reticulum to the cytosol in plant cells. Proc Natl Acad Sci USA 98:14726-14731

    Article  PubMed  Google Scholar 

  • 16. Ehrlich P (1891) Experimentelle Untersuchungen ueber Immunitaet. I. Ueber Ricin. Deutsche medizinische Wochenschrift, Berlin 17:976-979

    Google Scholar 

  • 17. 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 262:8128-8130

    CAS  PubMed  Google Scholar 

  • 18. Endo Y, Tsurugi K (1988) The RNA N-glycosidase activity of ricin A-chain. The characteristics of the enzymatic activity of ricin A-chain with ribosomes and with rRNA. J Biol Chem 263:8735-8739

    CAS  PubMed  Google Scholar 

  • 19. Ferrini JB, Martin M, Taupiac MP, Beaumelle B (1995) Expression of functional ricin B chain using the baculovirus system. Eur J Biochem 233:772-777

    CAS  PubMed  Google Scholar 

  • 20. Frigerio L, Jolliffe NA, Di Cola A, Felipe DH, Paris N, Neuhaus JM, Lord JM, Ceriotti A, Roberts LM (2001) The internal propeptide of the ricin precursor carries a sequence-specific determinant for vacuolar sorting. Plant Physiol 126:167-175

    Article  CAS  PubMed  Google Scholar 

  • 21. Frigerio L, Vitale A, Lord JM, Ceriotti A, Roberts LM (1998) Free ricin A chain, proricin, and native toxin have different cellular fates when expressed in tobacco protoplasts. J Biol Chem 273:14194-14199

    Article  CAS  PubMed  Google Scholar 

  • 22. Funatsu G, Kimura M, Funatsu M (1979) Primary structure of the Ala chain of ricin D. Agric Biol Chem 42:2221-2224

    Google Scholar 

  • 23. Funatsu G, Yoshitake S, Funatsu M (1978) Primart structure of the Ile chain of ricin D. Agric Biol Chem 42:501-503

    CAS  Google Scholar 

  • 24. Girod A, Storrie B, Simpson JC, Johannes L, Goud B, Roberts LM, Lord JM, Nilsson T, Pepperkok R (1999) Evidence for a COP-I-independent transport route from the Golgi complex to the endoplasmic reticulum. Nat Cell Biol 1:423-430

    Article  CAS  PubMed  Google Scholar 

  • 25. Griffiths G, Ericsson M, Krijnse-Locker J, Nilsson T, Goud B, Soling HD, Tang BL, Wong SH, Hong W (1994) Localization of the Lys, Asp, Glu, Leu tetrapeptide receptor to the Golgi complex and the intermediate compartment in mammalian cells. J Cell Biol 127:1557-1574

    Article  CAS  PubMed  Google Scholar 

  • 26. Grimmer S, van Deurs B, Sandvig K (2002) Membrane ruffling and macropinocytosis in A431 cells require cholesterol. J Cell Sci 115:2953-2962

    CAS  PubMed  Google Scholar 

  • 27. Halling KC, Halling AC, Murray EE, Ladin BF, Houston LL, Weaver RF (1985) Genomic cloning and characterization of a ricin gene from Ricinus communis. Nucl Acids Res 13:8019-8033

    CAS  PubMed  Google Scholar 

  • 28. Hara-Nishimura II, Shimada T, Hatano K, Takeuchi Y, Nishimura M (1998) Transport of storage proteins to protein storage vacuoles is mediated by large precursor-accumulating vesicles. Plant Cell 10:825-836

    Article  CAS  PubMed  Google Scholar 

  • 29. Harley SM, Beevers H (1982) Ricin inhibition of in vivo protein synthesis by plant ribosomes. Proc Natl Acad Sci USA 79:5935-5938

    CAS  Google Scholar 

  • 30. Harley SM, Lord JM (1985) In vitro endoproteolytic cleavage of castor bean lectin precursors. Plant Sci 41:111-116

    Article  CAS  Google Scholar 

  • 31. Hazes B, Read RJ (1997) Accumulating evidence suggests that several AB-toxins subvert the endoplasmic reticulum-associated protein degradation pathway to enter target cells. Biochemistry 36:11051-11054

    Article  CAS  PubMed  Google Scholar 

  • 32. Henley JR, Krueger EWA, Oswald BJ, McNiven MA (1998) Dynamin-mediated internalization of caveolae. J Cell Biol 141:85-89

    Article  CAS  PubMed  Google Scholar 

  • 33. Hirsch C, Blom D, Ploegh HL (1993) A role for N-glycanase in the cytosolic turnover of glycproteins. EMBO J 22:1036-1046

    Article  Google Scholar 

  • 34. Hirsch C, Misagi S, Blom D, Pacold ME, Ploegh HL (2004) Yeast N-glycanase distinguishes between native and non-native glycoproteins. EMBO Rep 5:201-206

    Article  CAS  PubMed  Google Scholar 

  • 35. Iversen TG, Skretting G, Llorente A, Nicoziani P, van Deurs B, Sandvig K (2001) Endosome to Golgi transport of ricin is independent of clathrin and of the Rab9- and Rab11-GTPases. Mol Biol Cell 12:2099-2107

    CAS  PubMed  Google Scholar 

  • 36. JO K, Albring J, Huter E, Bulbuc N, Spee P, Neefjes J, Hammerling G, Momburg F (2000) Export of antigenic peptides from the endoplasmic reticulum intersects with retrograde protein translocation through the Sec61p channel. Immunity 13:117-127

    Article  PubMed  Google Scholar 

  • 37. Johnson AE, van Maes MA (1999) The translocon: a dynamic gateway at the ER membrane. Annu Rev Cell Develop Biol 15:799-842

    Article  Google Scholar 

  • 38. Jolliffe NA, Ceriotti A, Frigerio L, Roberts LM (2003) The position of the proricin vacuolar targeting signal is functionally important. Plant Mol Biol 51:631-641

    Article  CAS  PubMed  Google Scholar 

  • 39. Katzin BJ, Collins EJ, Robertus JD (1991) Structure of ricin A-chain at 2.5 A. Proteins 10:251-259

    CAS  PubMed  Google Scholar 

  • 40. Koopman J, Albring J, Huter E, Bulbuc N, Spee P, Neefjes J, Hammerling G, Momburg F (2000) Export of antigenic peptides from the endoplasmic reticulum intersects with retrograde protein translocation through the Sec61p channel. Immunity 13:117-127

    Article  PubMed  Google Scholar 

  • 41. Lamaze C, Dujeancourt A, Baba T, Lo CG, Benmerah A, Dautry-Varsat A (2001) Interleukin 2 receptors and detergent-resistant membrane domains define a clathrin-independent endocytic pathway. Mol Cell 7:661-671

    Article  CAS  PubMed  Google Scholar 

  • 42. Lamb FI, Roberts LM, Lord JM (1985) Nucleotide sequence of cloned cDNA coding for preproricin. Eur J Biochem 148:265-270

    CAS  PubMed  Google Scholar 

  • 43. Lewis MS, Youle RJ (1986) Ricin subunit association. Thermodynamics and the role of the disulfide bond in toxicity. J Biol Chem 261:11571-11577

    CAS  PubMed  Google Scholar 

  • 44. Llorente A, Lauvrak SU, Van Deurs B, Sandvig K (2003) Induction of direct endosome to endoplasmic reticulum transport in Chinese hamster ovary (CHO) cells (LdlF) with a temperature-sensitive defect in epsilon-coatomer protein (epsilon-COP). J Biol Chem 278:35850-35855

    Article  CAS  PubMed  Google Scholar 

  • 45. Llorente A, Rapak A, Schmid SL, van Deurs B, Sandvig K (1998) Expression of mutant dynamin inhibits toxicity and transport of endocytosed ricin to the Golgi apparatus. J Cell Biol 140:553-563

    Article  CAS  PubMed  Google Scholar 

  • 46. Lombardi D, Soldati T, Riederer MA, Goda Y, Zerial M, Pfeffer SR (1993) Rab9 functions in transport between late endosomes and the trans Golgi network. EMBO J 12:677-682

    CAS  PubMed  Google Scholar 

  • 47. Lord JM (1985a) Precursors of ricin and Ricinus communis agglutinin. Glycosylation and processing during synthesis and intracellular transport. Eur J Biochem 146:411-416

    CAS  PubMed  Google Scholar 

  • 48. Lord JM (1985b) Synthesis and intracellular transport of lectin and storage protein precursors in endosperm from castor bean. Eur J Biochem 146:403-409

    CAS  PubMed  Google Scholar 

  • 49. Lord JM, Harley SM (1985) Ricinus communis agglutinin B chain contains a fucosylated oligosaccharide side chain not present on ricin B chain. FEBS Lett 189:72-76

    Article  CAS  Google Scholar 

  • 50. Magnusson S, Kjeken R, Berg T (1993) Characterization of two distinct pathways of endocytosis of ricin by rat liver endothelial cells. Expl Cell Res 205:118-125

    Article  CAS  Google Scholar 

  • 51. Majoul I, Ferrari D, Soling HD (1997) Reduction of protein disulfide bonds in an oxidizing environment. The disulfide bridge of cholera toxin A-subunit is reduced in the endoplasmic reticulum. FEBS Lett 401:104-108

    Article  CAS  PubMed  Google Scholar 

  • 52. Mallard F, Antony C, Tenza D, Salamero J, Goud B, Johannes L (1998) Direct pathway from early/recycling endosomes to the Golgi apparatus revealed through the study of shiga toxin B-fragment transport. J Cell Biol 143:973-990

    Article  CAS  PubMed  Google Scholar 

  • 53. Mallard F, Johannes L (2003) Shiga toxin B-subunit as a tool to study retrograde transport. Methods Mol Med 73:209-220

    CAS  PubMed  Google Scholar 

  • 54. Mallard F, Tang BL, Galli T, Tenza D, Saint-Pol A, Yue X, Antony C, Hong W, Goud B, Johannes L (2002) Early/recycling endosomes-to-TGN transport involves two SNARE complexes and a Rab6 isoform. J Cell Biol 156:653-664

    Article  CAS  PubMed  Google Scholar 

  • 55. Mallet WG, Maxfield FR (1999) Chimeric forms of furin and TGN38 are transported with the plasma membrane in the trans-Golgi network via distinct endosomal pathways. J Cell Biol 146:345-359

    Article  CAS  PubMed  Google Scholar 

  • 56. Marsden CJ, Knight S, Smith DC, Day PJ, Roberts LM, Phillips GJ, Lord JM (2004) Insertional mutagenesis of ricin A chain: a novel route to an anti-ricin vaccine. Vaccine (in press)

    Google Scholar 

  • 57. McKee ML, FitzGerald DJ (1999) Reduction of furin-nicked Pseudomonas exotoxin A: an unfolding story. Biochemistry 38:16507-16513

    Article  CAS  PubMed  Google Scholar 

  • 58. Mlsna D, Monzingo AF, Katzin BJ, Ernst S, Robertus JD (1993) Structure of recombinant ricin A chain at 2.3 A. Protein Sci 2:429-435

    CAS  PubMed  Google Scholar 

  • 59. Moazed D, Robertson JM, Noller HF (1988) Interaction of elongation factors EF-G and EF-Tu with a conserved loop in 23S RNA. Nature 334:362-364

    Article  CAS  PubMed  Google Scholar 

  • 60. Montfort W, Villafranca JE, Monzingo AF, Ernst SR, Katzin B, Rutenber E, Xuong NH, Hamlin R, Robertus JD (1987) The three-dimensional structure of ricin at 2.8 A. J Biol Chem 262:5398-5403

    CAS  PubMed  Google Scholar 

  • 61. Monzingo AF, Robertus JD (1992) X-ray analysis of substrate analogs in the ricin A-chain active site. J Mol Biol 227:1136-1145

    CAS  PubMed  Google Scholar 

  • 62. Morlon-Guyot J, Helmy M, Lombard-Frasca S, Pignol D, Pieroni G, Beaumelle B (2003) Identification of the ricin lipase site and implication in cytotoxicity. J Biol Chem 278:17006-17011

    Article  CAS  PubMed  Google Scholar 

  • 63. Moya M, Dautry-Varsat A, Goud B, Louvard D, Boquet P (1985) Inhibition of coated pit formation in Hep2 cells blocks the cytotoxicity of diphtheria toxin but not that of ricin toxin. J Cell Biol 101:548-559

    Article  CAS  PubMed  Google Scholar 

  • 64. Namibar MP, Wu HC (1995) Ilimaquinone inhibits the cytotoxicities of ricin, diphtheria toxin and other protein toxins in Vero cells. Expl Cell Res 219:671-678

    Article  Google Scholar 

  • 65. Newton DL, Wales R, Richardson PT, Walbridge S, Saxena SK, Ackerman EJ, Roberts LM, Lord JM, Youle RJ (1992) Cell surface and intracellular functions for ricin galactose binding. J Biol Chem 267:11917-11922

    CAS  PubMed  Google Scholar 

  • 66. Nichols BJ, Kenworthy AK, Polishchuk RS, Lodge R, Roberts TH, Hirschberg K, Phair RD, Lippincott-Schwartz J (2001) Rapid cycling of lipid raft markers between the cell surface and Golgi complex. J Cell Biol 153:529-541

    Article  CAS  PubMed  Google Scholar 

  • 67. Nichols BJ, Lippincott-Schwartz J (2001) Endocytosis without clathrin coats. Trends Cell Biol 11:406-412

    Article  CAS  PubMed  Google Scholar 

  • 68. Nilsson L, Nygard O (1986) The mechanism of the protein synthesis elongation cycle in eukaryotes: the effects of ricin on the ribosome interaction with elongation factors. Eur J Biochem 161:111-117

    CAS  PubMed  Google Scholar 

  • 69. Oh P, McIntosh DP, Schnitzer JE (1998) Dynamin at the necks of caveolae mediates their budding to form transport vesicles by GTP-driven fission from the plasma membrane of endothelium. J Cell Biol 141:101-114

    Article  CAS  PubMed  Google Scholar 

  • 70. Olsnes S (1978) Ricin and ricinus agglutinin, toxic lectins from castor bean. Methods Enzymol 50:330-335

    Article  CAS  PubMed  Google Scholar 

  • 71. Olsnes S, Pihl A (1982) Toxic lectins and related proteins. In Cohen P, van Heyningen S, editors. Molecular action of toxins and viruses. Amsterdam, Elsevier, pp. 51-105

    Google Scholar 

  • 72. Orlandi PA (1997) Protein-disulfide isomerase-mediated reduction of the A subunit of cholera toxin in a human intestinal cell line. J Biol Chem 272:4591-4599

    CAS  PubMed  Google Scholar 

  • 73. Pelham HRB, Roberts LM, Lord JM (1992) Toxin entry: how reversible is the secretory pathway? Trends Cell Biol 2:183-185

    Article  CAS  PubMed  Google Scholar 

  • 74. Pelkmans L, Kartenbeck J, Helenius A (2001) Caveolar endocytosis of simian virus 40 reveals a new two-step vesicular-transport pathway to the ER. Nat Cell Biol 3:473-483

    Article  CAS  PubMed  Google Scholar 

  • 75. Prydz K, Hansen SH, Sandvig K, van Deurs B (1992) Effects of brefeldin A on endocytosis, transcytosis and transport to the Golgi complex in polarized MDCK cells. J Cell Biol 119:259-272

    Article  CAS  PubMed  Google Scholar 

  • 76. Rapak A, Falnes PO, Olsnes S (1997) Retrograde transport of mutant ricin to the endoplasmic reticulum with subsequent translocation to cytosol. Proc Natl Acad Sci USA 94:3783-3788

    Article  CAS  PubMed  Google Scholar 

  • 77. Richardson PT, Westby M, Roberts LM, Gould JH, Colman A, Lord JM (1989) Recombinant proricin binds galactose but does not depurinate 28 S ribosomal RNA. FEBS Lett 255:15-20

    Article  CAS  PubMed  Google Scholar 

  • 78. Riederer MA, Soldati T, Shapiro AD, Goda Y, Zerial M, Pfeffer S (1994) Lysosome biogenesis requires Rab9 function and receptor recycling from late endosomes to the trans-Golgi network. J Cell Biol 125:573-582

    Article  CAS  PubMed  Google Scholar 

  • 79. Roberts LM, Lord JM (1981) The synthesis of Ricinus communis agglutinin, cotranslational and posttranslational modification of agglutinin polypeptides. Eur J Biochem 119:31-41

    CAS  PubMed  Google Scholar 

  • 80. Rodal SK, Skretting G, Garred O, Vilhardt F, van Deurs B, Sandvig K (1999) Extraction of cholesterol with methyl-beta-cyclodextrin perturbs formation of clathrin-coated endocytic vesicles. Mol Biol Cell 10:961-974

    CAS  PubMed  Google Scholar 

  • 81. Rodighiero C, Tsai B, Rapoport TA, Lencer WI (2002) Role of ubiquitination in retro-translocation of cholera toxin and escape of cytosolic degradation. EMBO Rep 3:1222-1227

    Article  CAS  PubMed  Google Scholar 

  • 82. Romisch K, Ali BR (1997) Similar processes mediate glycopeptide export from the endoplasmic reticulum in mammalian cells and Saccharomyces cerevisiae. Proc Natl Acad Sci USA 94:6730-6734

    Article  CAS  PubMed  Google Scholar 

  • 83. Russ G, Esquivel F, Yewdell JW, Cresswell P, Spies T, Bennink JR (1995) Assembly, intracellular location and nucleotide binding properties of the human peptide transporters TAP1 and TAP2 expressed by recombinant vaccinia viruses. J Biol Chem 270:21312-21318

    Article  CAS  PubMed  Google Scholar 

  • 84. Sandvig K, Grimmer S, Lauvrak SU, Torgersen ML, Skretting G, van Deurs B, Iversen TG (2002) Pathways followed by ricin and Shiga toxin into cells. Histochem Cell Biol 117:131-141

    Article  CAS  PubMed  Google Scholar 

  • 85. Sandvig K, Olsnes S, Petersen OW, van Deurs B (1987) Acidification of the cytosol inhibits endocytosis from coated pits. J Cell Biol 105:679-689

    Article  CAS  PubMed  Google Scholar 

  • 86. Sandvig K, Olsnes S, Pihl A (1976) Kinetics of binding of the toxic lectins abrin and ricin to surface receptors of human cells. J Biol Chem 251:3977-3984

    CAS  PubMed  Google Scholar 

  • 87. Sandvig K, Prydz K, Hansen SH, van Deurs B (1991) Ricin transport in brefeldin A-treated cells: correlation between Golgi structure and toxic effect. J Cell Biol 115:971-981

    Article  CAS  PubMed  Google Scholar 

  • 88. Sandvig K, van Deurs B (1996) Endocytosis, intracellular transport, and cytotoxic action of Shiga toxin and ricin. Physiol Rev 76:949-966

    CAS  PubMed  Google Scholar 

  • 89. Sandvig K, van Deurs B (2002) Transport of protein toxins into cells: pathways used by ricin, cholera toxin and Shiga toxin. FEBS Lett 529:49-53

    Article  CAS  PubMed  Google Scholar 

  • 90. Schmitz A, Herrgen H, Winkeler A, Herzog V (2000) Cholera toxin is exported from microsomesby the Sec61p complex. J Cell Biol 148:1203-1212

    Article  CAS  PubMed  Google Scholar 

  • 91. Simmons BM, Stahl PD, Russell JH (1986) Mannose-receptor mediated uptake of ricin toxin and ricin A chain by macrophages. Multiple intracellular pathways for A chain translocation. J Biol Chem 261:7912-7920

    CAS  PubMed  Google Scholar 

  • 92. Simpson JC, Dascher C, Roberts LM, Lord JM, Balch WE (1995) Ricin cytotoxicity is sensitive to recycling between the endoplasmic reticulum and the Golgi complex. J Biol Chem 270:20078-20083

    Article  CAS  PubMed  Google Scholar 

  • 93. Smith DC, Gallimore A, Jones E, Roberts B, Lord JM, Deeks E, Cerundolo V, Roberts LM (2002) Exogenous peptides delivered by ricin require processing by signal peptidase for transporter associated with antigen processing-independent MHC class I-restricted presentation. J Immunol 169:99-107

    CAS  PubMed  Google Scholar 

  • 94. Sommer T, Wolf DH (1997) Endoplasmic reticulum degradation: reverse protein flow of no return. FASEB J 11:1227-1233

    CAS  PubMed  Google Scholar 

  • 95. Spilsberg B, Van Meer G, Sandvig K (2003) Role of lipids in the retrograde pathway of ricin intoxication. Traffic 4:544-552

    CAS  PubMed  Google Scholar 

  • 96. Stillmark H (1888) Über Ricin, ein giftiges Ferment aus den Samen von Ricinus communis L. und anderen Euphorbiacen. Doctoral Thesis, University of Estonia

    Google Scholar 

  • 97. Suzuki T, Park H, Hollingsworth NM, Sternglanz R, Lennarz WJ (2000) PNG1, a yeast gene encoding a highly conserved peptide:N-glycanase. J Cell Biol 149:1039-1052

    Article  CAS  PubMed  Google Scholar 

  • 98. Suzuki T, Park H, Lennarz WJ (2002) Cytoplasmic peptide:N-glycanase (PNGase) in eukaryotic cells: occurrence, primary structure and potential functions. FASEB J 16:635-641

    Article  CAS  PubMed  Google Scholar 

  • 99. Szewczak AA, Moore PB, Chang YL, Wool IG (1993) The conformation of the sarcin/ricin loop from 28S ribosomal RNA. Proc Natl Acad Sci USA 90:9581-9585

    CAS  PubMed  Google Scholar 

  • 100. Taylor S, Massiah A, Lomonossoff G, Roberts LM, Lord JM, Hartley M (1994) Correlation between the activities of five ribosome-inactivating proteins in depurination of tobacco ribosomes and inhibition of tobacco mosaic virus infection. Plant J 5:827-835

    Article  CAS  PubMed  Google Scholar 

  • 101. Teter K, Holmes RK (2002) Inhibition of endoplasmic reticulum-associated degradation in CHO cells resistant to cholera toxin, Pseudomonas aeruginosa exotoxin A, and ricin. Infect Immun 70:6172-6179

    Article  CAS  PubMed  Google Scholar 

  • 102. Tregear JW, Roberts LM (1992) The lectin gene family of Ricinus communis: cloning of a functional ricin gene and three lectin pseudogenes. Plant Mol Biol 18:515-525

    CAS  PubMed  Google Scholar 

  • 103. Tsai B, Rodighiero C, Lencer WI, Rapoport TA (2001) Protein disulfide isomerase acts as a redox-dependent chaperone to unfold cholera toxin. Cell 104:937-948

    Article  CAS  PubMed  Google Scholar 

  • 104. Tsai B, Ye Y, Rapoport TA (2002) Retro-translocation of proteins from the endoplasmic reticulum into the cytosol. Nat Rev Mol Cell Biol 3:246-255

    Article  CAS  PubMed  Google Scholar 

  • 105. Tulley RE, Beevers H (1976) Protein bodies of castor bean endosperm. Isolation, fractionation, and characterization of protein components. Plant Physiol 58:710-716

    Google Scholar 

  • 106. van Deurs B, Pedersen LR, Sundan A, Olsnes S, Sandvig K (1985) Receptor-mediated endocytosis of a ricin-colloidal gold conjugate in vero cells. Intracellular routing to vacuolar and tubulo-vesicular portions of the endosomal system. Expl Cell Res 159:287-304

    Google Scholar 

  • 107. van Deurs B, Sandvig K, Petersen OW, Olsnes S, Simons K, Griffiths G (1988) Estimation of the amount of internalized ricin that reaches the trans-Golgi network. J Cell Biol 106:253-267

    Article  PubMed  Google Scholar 

  • 108. Villafranca JE, Robertus JD (1981) Ricin B chain is a product of gene duplication. J Biol Chem 256:554-556

    CAS  PubMed  Google Scholar 

  • 109. Vitale A, Raikhel N (1999) What do proteins need to reach different vacuoles? Trends Plant Sci 4:149-155

    Article  PubMed  Google Scholar 

  • 110. Wales R, Chaddock JA, Roberts LM, Lord JM (1992) Addition of an ER retention signal to the ricin A chain increases the cytotoxicity of the holotoxin. Expl Cell Res 203:1-4

    CAS  Google Scholar 

  • 111. Wales R, Roberts LM, Lord JM (1993) Addition of an endoplasmic reticulum retrieval sequence to ricin A chain significantly increases its cytotoxicity to mammalian cells. J Biol Chem 268:23986-23990

    CAS  PubMed  Google Scholar 

  • 112. Wesche J, Rapak A, Olsnes S (1999) Dependence of ricin toxicity on translocation of the toxin A-chain from the endoplasmic reticulum to the cytosol. J Biol Chem 274:34443-34449

    Article  CAS  PubMed  Google Scholar 

  • 113. Weston SA, Tucker AD, Thatcher DR, Derbyshire DJ, Paupit RA (1994) X-ray structure of recombinant ricin A chain at 1.8 Å resolution. J Mol Biol 244:410-422

    Article  CAS  PubMed  Google Scholar 

  • 114. Wright HT, Robertus JD (1987) The intersubunit disulfide bridge of ricin is essential for cytotoxicity. Arch Biochem Biophys 256:280-284

    CAS  PubMed  Google Scholar 

  • 115. Yoshida T, Chen CC, Zhang MS, Wu HC (1991) Disruption of the Golgi apparatus by brefeldin A inhibits the cytotoxicity of ricin, modeccin, and Pseudomonas toxin. Expl Cell Res 192:389-395

    CAS  Google Scholar 

  • 116. Youle RJ, Huang AHC (1976) Protein bodies from castor bean endosperm. Subfractionation, protein components, lectins, and changes during germination. Plant Physiol 58:703-709

    CAS  Google Scholar 

  • 117. Zhan J, Stayton P, Peress OW (1998) Modification of ricin A chain, by addition of endoplasmic reticulum (KDEL) or Golgi (YQRL) retention sequences, enhances its sensitivity and translocation. Cancer Immunol Immunother 46:55-60

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Editor information

Manfred J. Schmitt Raffael Schaffrath

Rights and permissions

Reprints and permissions

About this chapter

Cite this chapter

Lord, J.M., Roberts, L.M. Ricin: structure, synthesis, and mode of action. In: Schmitt, M.J., Schaffrath, R. (eds) Microbial Protein Toxins. Topics in Current Genetics, vol 11. Springer, Berlin, Heidelberg. https://doi.org/10.1007/b100198

Download citation

Publish with us

Policies and ethics