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Enzymatic Activities of Ribosome-Inactivating Proteins

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Book cover Toxic Plant Proteins

Part of the book series: Plant Cell Monographs ((CELLMONO,volume 18))

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Abstract

Ribosome-inactivating proteins (RIPs) constitute a diverse group of proteins that share an RNA N-glycosidase activity that acts very specifically on the ribosomal RNA of the 50S/60S ribosomal subunit to inhibit protein synthesis. Additionally, the majority of RIPs act on non-ribosomal RNA and DNA in a sequence context-independent fashion, releasing multiple adenines and sometimes guanines. One such activity depends on the presence of a 5′ cap structure, and may be responsible for the anti-viral properties of some RIPs. In addition to their N-glycosidase activity on nucleic acids, some ribosome-inactivating enzymes have been reported to be bifunctional with another, unrelated activity. No active sites for these unrelated activities have been found, and their presence in preparations of RIPs may be due to contamination.

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References

  • Ayub MJ, Smulski CR, Ma K-W, Levin MJ, Shaw P-C, Wong K-B (2008) The C-terminal end of P proteins mediates ribosome inactivation by trichosanthin but does not affect the pokeweed antiviral protein activity. Biochem Biophys Res Commun 369:314–319

    Article  PubMed  CAS  Google Scholar 

  • Barbieri L, Ferreras JM, Baracco A, Ricci P, Stirpe F (1992) Some ribosome-inactivating proteins depurinate ribosomal RNA at multiple sites. Biochem J 286:1–4

    PubMed  CAS  Google Scholar 

  • 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  PubMed  CAS  Google Scholar 

  • Chan DSB, Chu L-O, Lee K-M, Too PHM, Ma K-W, Sze K-H, Zhu G, Shaw P-C, Wong K-B (1997) Interaction between trichosanthin, a ribosome-inactivating protein, and the ribosomal stalk protein P2 by chemical shift perturbation and mutagenesis analysis. Nucleic Acids Res 35:1660–1672

    Article  Google Scholar 

  • Chiou J-C, Li X-P, Remache M, Ballestra JPG, Tumer NE (2008) The ribosomal stalk is required for ribosome binding, depurination of the rRNA and cytotoxicity of ricin A-chain in Saccharomyces cerevisiae. Mol Microbiol 70:1441–1452

    Article  PubMed  CAS  Google Scholar 

  • Endo Y, Tsurugi K (1987) The RNA N-glycosidase of ricin A-chain. Mechanism of action of the toxic lectin on eukaryotic ribosomes. J Biol Chem 262:8128–8130

    PubMed  CAS  Google Scholar 

  • 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 rRNA. J Biol Chem 263:8735–8739

    PubMed  CAS  Google Scholar 

  • Endo Y, Mitsui K, Motizuki M, Tsurugi K (1987) The mechanism of action of ricin and related toxic lectins on eukaryotic ribosomes. The site and characteristics of the modification in 28S ribosomal RNA caused by the toxins. J Biol Chem 262:5908–5912

    PubMed  CAS  Google Scholar 

  • Endo Y, Gluck A, Wool IG (1991) Ribosomal RNA identity elements for ricin A-chain recognition and catalysis. J Mol Biol 221:193–207

    Article  PubMed  CAS  Google Scholar 

  • Endo Y, Tsurugi K, Lambert JM (1998) The site of action of six different ribosome-inactivating proteins from plants on eukaryotic ribosomes: the RNA N-glycosidase activity of the proteins. Biochem Biophys Res Commun 150:1032–1036

    Article  Google Scholar 

  • Girbés T, Ferreras JM, Arias FJ, Stirpe F (2004) Description, distribution, activity and phylogenetic relationship of ribosome-inactivating proteins in plants, fungi and bacteria. Mini Rev Med Chem 4:461–476

    Article  PubMed  Google Scholar 

  • Heldt HW (1997) Plant biochemistry and molecular biology. Oxford University Press, Oxford

    Google Scholar 

  • Helgstrand M, Mandava CS, Mulder FAA, Liljas A, Sanyl S, Akke M (2007) The ribosomal stalk binds to translation factors IF2, EF-Tu, EF-G and RF3 via a conserved region of the L12 C-terminal domain. J Mol Biol 365:468–479

    Article  PubMed  CAS  Google Scholar 

  • Hudak KA, Dinman JD, Tumer NE (1999) Pokeweed antiviral protein accesses ribosomes by binding to L3. J Biol Chem 274:3859–3864

    Article  PubMed  CAS  Google Scholar 

  • Hudak KA, Wang P, Tumer NE (2000) A novel mechanism for inhibition of translation by pokeweed antiviral protein: depurination of the capped RNA template. RNA 6:369–380

    Article  PubMed  CAS  Google Scholar 

  • Hudak KA, Bauman JD, Tumer NE (2002) Pokeweed antiviral protein binds to the cap structure of eukaryotic mRNA and depurinates the mRNA downstream of the cap. RNA 8:1148–1159

    Article  PubMed  CAS  Google Scholar 

  • Hudak KA, Parikh BA, Di R, Baricevic M, Santana M, Seskar M, Tumer NE (2004) Generation of pokeweed antiviral mutations in Saccharomyces cerevisiae: evidence that ribosome depurination is not sufficient for cytotoxicity. Nucleic Acids Res 32:4244–4256

    Article  PubMed  CAS  Google Scholar 

  • Korennykh AV, Correll CC, Piccirilli JA (2007) Evidence for the importance of electrostatics in the function of two distinct families of ribosome inactivating toxins. RNA 13:1391–1396

    Article  PubMed  CAS  Google Scholar 

  • Leah R, Tommerup H, Svendsen I, Mundy J (1991) Biochemical and molecular characterization of three barley seed proteins with antifungal properties. J Biol Chem 266:1564–1573

    PubMed  CAS  Google Scholar 

  • Lodge JK, Kaniewski WK, Tumer NE (1993) Broad-spectrum virus resistance in transgenic plants expressing pokeweed antiviral protein. Proc Natl Acad Sci USA 90:7089–7093

    Article  PubMed  CAS  Google Scholar 

  • Lombard S, Helmy ME, Pieroni G (2001) Lipolytic activity of ricin from Ricinus sanguineus and Ricinus communis on neutral lipids. Biochem J 358:773–781

    Article  PubMed  CAS  Google Scholar 

  • Marchant A, Hartley MR (1994) Mutational studies on the α-sarcin loop of Escherichia coli 23S ribosomal RNA. Eur J Biochem 226:141–147

    Article  PubMed  CAS  Google Scholar 

  • Marchant A, Hartley MR (1995) The action of pokeweed antiviral protein and ricin A-chain on mutants in the α-sarcin loop of Escherichia coli 23S ribosomal RNA. J Mol Biol 254:848–855

    Article  PubMed  CAS  Google Scholar 

  • Massiah AJ, Hartley MR (1995) Wheat ribosome-inactivating proteins: seed and leaf forms with different specificities and cofactor requirements. Planta 197:633–640

    Article  PubMed  CAS  Google Scholar 

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

    Article  Google Scholar 

  • Moulin A, Teissere M, Bernard C, Pieroni G (1994) Lipases of the Euphorbiaceae family: purification of a lipase from Euphorbia characias latex and structure–function relationships with ricin B chain. Proc Natl Acad Sci USA 91:11328–11332

    Article  PubMed  CAS  Google Scholar 

  • Nicolas E, Beggs JM, Haltiwanger BM, Taraschi TF (1998) A new class of DNA glycosylase apurinic/apyrimidinic lyases that act on specific adenines in single-stranded DNA. Biol Chem 273:17216–17220

    Article  CAS  Google Scholar 

  • Olsnes S, Pihl A (1982) Toxic lectins and related proteins. In: Cohen P, van Heyringen J (eds) Molecular action of toxins and viruses. Elsevier, Amsterdam, pp 51–105

    Chapter  Google Scholar 

  • Osborn RW, Hartley MR (1990) Dual effects of the ricin A-chain on protein synthesis in rabbit reticulocyte lysate. Eur J Biochem 193:401–407

    Article  PubMed  CAS  Google Scholar 

  • Parikh BA, Coetzert C, Tumer NE (2002) Pokeweed antiviral protein regulates the stability of its own mRNA by a mechanism that requires depurination but can be separated from depurination of the α-sarcin/ricin loop of rRNA. J Biol Chem 44:41428–41437

    Article  Google Scholar 

  • Parikh BA, Baykal U, Tumer NE (2005) Evidence for retro-translocation of pokeweed antiviral protein from endoplasmic reticulum into cytosol and separation of its activity on ribosomes from its activity on capped RNA. Biochemistry 44:2478–2490

    Article  PubMed  CAS  Google Scholar 

  • Park S-W, Vepachedu R, Owens RA, Vivanco JM (2004) The N-glycosidase activity of the ribosome-inactivating protein ME1 targets single-stranded regions of nucleic acids independent of sequence or structural motifs. J Biol Chem 279:34165–34174

    Article  PubMed  CAS  Google Scholar 

  • Peumans WJ, Hao Q, Van Damme EJM (2001) Ribosome-inactivating proteins from plants: more than RNA N-glycosidases? FASEB J 15:1493–1506

    Article  PubMed  CAS  Google Scholar 

  • Prestel J, Schönfelder M, Adam G, Mundry K (1992) Type1 ribosome-inactivating proteins depurinate plant 25S rRNA without species specificity. Nucleic Acids Res 20(12):3179–3182

    Article  Google Scholar 

  • Rajamohan F, Kurinov IV, Venkatachalam TK, Ukun FM (1999a) Deguanylation of human immunodeficiency virus (HIV-1) RNA by recombinant pokeweed antiviral protein. Biochem Biophys Res Commun 263:419–424

    Article  PubMed  CAS  Google Scholar 

  • Rajamohan F, Venkatachalam TK, Irvin JD, Uckun FM (1999b) Pokeweed antiviral protein isoforms PAP-I, PAP-II and PAP-III depurinate RNA of human immunodeficiency virus (HIV)-1. Biochem Biophys Res Commun 260:453–459

    Article  PubMed  CAS  Google Scholar 

  • Robertus JD, Monzingo AF (2004) The structure of ribosome inactivating proteins. Mini Rev Med Chem 4:477–486

    Article  PubMed  CAS  Google Scholar 

  • Sharma N, Park S-W, Vepachedu R, Barbieri L, Ciani M, Stirpe F, Savary BJ, Vivanco JM (2004) Isolation and characterization of an RIP (ribosome-inactivating protein)-like protein from tobacco with dual enzymatic activity. Plant Physiol 134:171–181

    Article  PubMed  CAS  Google Scholar 

  • Shih NR, McDonald KA, Jackman AP, Girbés T, Iglesias R (1997) Bifunctional plant defence enzymes with chitinase and ribosome inactivating activities from Trichosanthes kirilowii cell cultures. Plant Sci 130:145–150

    Article  CAS  Google Scholar 

  • Sikriwal D, Ghosh P, Batra JK (2008) Ribosome inactivating protein saporin induces apoptosis through mitochondrial cascade independent of translation inhibition. Int J Biochem Cell Biol 40:2880–2888

    Article  PubMed  CAS  Google Scholar 

  • Taylor BE, Irvin JD (1990) Depurination of plant ribosomes by pokeweed antiviral protein. FEBS Lett 273:144–146

    Article  PubMed  CAS  Google Scholar 

  • Too PH-I, Ma MK-W, Mak AN-S, Wong Y-T, Tung K-CT, Zhu G, Au SW-N, Wong K-B, Shaw PC (2009) The C-terminal fragment of the ribosomal P protein complexed to trichosanthin reveals the interaction between the ribosome-inactivating protein and the ribosome. Nucleic Acids Res 37:602–610

    Article  PubMed  CAS  Google Scholar 

  • Tumer NE, Hwang D-J, Bonness M (1997) C-terminal deletion mutant of pokeweed antiviral protein inhibits viral infection but does not depurinate host ribosomes. Proc Natl Acad Sci USA 94:3866–3871

    Article  PubMed  CAS  Google Scholar 

  • Wang Y-X, Neamati JJ, Palmer I, Stahl SJ, Kaufman JD, Huang PL, Huang PL, Winslow HE, Pommier Y, Wingfield PT, Lee-Hang S, Bax A, Torchia DA (1999) Solution structure of anti-HIV-1 and anti-tumor protein MAP30: structural insights into its multiple functions. Cell 99:433–442

    Article  PubMed  CAS  Google Scholar 

  • Wool IG, Correll CC, Chan Y-L (2000) Structure and function of the sarcin–ricin domain. In: Garrett RA, Douthwaite SR, Liljas A, Marteson AT, Moore PB, Noller HF (eds) The ribosome: structure, function, antibiotics and cellular interactions. ASM, Washington

    Google Scholar 

  • Zoubenko O, Ukun F, Hur Y, Chet I, Tumer N (1997) Plant resistance to fungal infection induced by nontoxic pokeweed antiviral protein mutants. Nat Biotechnol 15:992–996

    Article  PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Department of Biological Sciences, University of Warwick, Coventry, CV4 7AL, UK

    Martin R. Hartley

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  1. Martin R. Hartley
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Correspondence to Martin R. Hartley .

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Editors and Affiliations

  1. Dept. Biological Sciences, University of Warwick, Coventry, CV47AL, United Kingdom

    J. Michael Lord

  2. Dept. Biological Sciences, University of Warwick, Coventry, CV47AL, United Kingdom

    Martin R. Hartley

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Hartley, M.R. (2010). Enzymatic Activities of Ribosome-Inactivating Proteins. In: Lord, J., Hartley, M. (eds) Toxic Plant Proteins. Plant Cell Monographs, vol 18. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-12176-0_3

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