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Endogenous ADP-Ribosylation pp 33–50Cite as

Identification and Analysis of ADP-Ribosylated Proteins

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Part of the book series: Current Topics in Microbiology and Immunology ((CT MICROBIOLOGY,volume 384))

Abstract

The analysis of ADP-ribosylated proteins is a challenging task, on the one hand because of the diversity of the target proteins and the modification sites, on the other hand because of the particular problems posed by the analysis of ADP-ribosylated peptides. ADP-ribosylated proteins can be detected in in vitro experiments after the incorporation of radioactively labeled or chemically modified ADP-ribose. Endogenously ADP-ribosylated proteins may be detected and enriched by antibodies directed against the ADP-ribosyl moiety or by ADP-ribosyl binding macro domains. The determination of the exact attachment site of the modification, which is a prerequisite for the understanding of the specificity of the various ADP-ribosyl transferases and the structural consequences of ADP-ribosylation, necessitates the proteolytic cleavage of the proteins. The resulting peptides can afterwards be enriched either by IMAC (using the affinity of the pyrophosphate group for heavy metal ions) or by immobilized boronic acid beads (using the affinity of the vicinal ribose hydroxy groups for boronic acid). The identification of the modified peptides usually requires tandem mass spectrometric measurements. Problems that hamper the mass spectrometric analysis by collision-induced decay (CID) can be circumvented either by the application of different fragmentation techniques (electron transfer or electron capture dissociation; ETD or ECD) or by enzymatic cleavage of the ADP-ribosyl group to ribosyl-phosphate.

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Abbreviations

ADP:

Adenosine diphosphate

CID:

Collision-induced decay

IMAC:

Immobilized metal ion affinity chromatography

ECD:

Electron capture dissociation

ETD:

Electron transfer dissociation

GAPDH:

Glyceraldehyde-3-phosphate dehydrogenase

HNP-1:

Human neutrophil peptide-1

LC/MS:

Liquid chromatography/mass spectrometry

MS/MS:

Tandem mass spectrometry

NAD:

Nicotinamide adenine dinucleotide

QTOF:

Quadrupol time-of-flight

SDS-PAGE:

Sodium dodecyl sulfate polyacrylamide gel electrophoresis

References

  • Armstrong S, Merrill AR (2001) Application of a fluorometric assay for characterization of the catalytic competency of a domain III fragment of Pseudomonas aeruginosa exotoxin A. Anal Biochem 292:26–33

    Article  PubMed  CAS  Google Scholar 

  • Bannas P, Adriouch S, Kahl S, Braasch F, Haag F, Koch-Nolte F (2005) Activity and specificity of toxin-related mouse T cell ecto-ADP-ribosyltransferase ART2.2 depends on its association with lipid rafts. Blood 105:3663–3670

    Article  PubMed  CAS  Google Scholar 

  • Bannas P, Graumann O, Balcerak P, Peldschus K, Kaul MG, Hohenberg H, Haag F, Adam G, Ittrich H, Koch-Nolte F (2010) Quantitative magnetic resonance imaging of enzyme activity on the cell surface: in vitro and in vivo monitoring of ADP-ribosyltransferase 2 on T cells. Mol Imaging 9:211–222

    PubMed  CAS  Google Scholar 

  • Carapito C, Klemm C, Aebersold R, Domon B (2009) Systematic LC-MS analysis of labile post-translational modifications in complex mixtures. J Proteome Res 8:2608–2614

    Article  PubMed  CAS  Google Scholar 

  • Cervantes-Laurean D, Jacobson EL, Jacobson MK (1997) Preparation of low molecular weight model conjugates for ADP-ribose linkages to protein. Methods Enzymol 280:275–287

    Article  PubMed  CAS  Google Scholar 

  • Cervantes-Laurean D, Minter DE, Jacobson EL, Jacobson MK (1993) Protein glycation by ADP-ribose: studies of model conjugates. Biochemistry 32:1528–1534

    Article  PubMed  CAS  Google Scholar 

  • Chambon P, Weill JD, Doly J, Strosser MT, Mandel P (1966) On the formation of a novel adenylic compound by enzymatic extracts of liver nuclei. Biochem Biophys Res Commun 25:638–643

    Article  CAS  Google Scholar 

  • Chambon P, Weill JD, Mandel P (1963) Nicotinamide mononucleotide activation of new DNA-dependent polyadenylic acid synthesizing nuclear enzyme. Biochem Biophys Res Commun 11:39–43

    Article  PubMed  CAS  Google Scholar 

  • Chapman JD, Gagne JP, Poirier GG, Goodlett DR (2013) Mapping PARP-1 Auto-ADP-ribosylation sites by liquid chromatography-Tandem Mass Spectrometry. J Proteome Res 12(4):1868–1880

    Google Scholar 

  • Dani N, Stilla A, Marchegiani A, Tamburro A, Till S, Ladurner AG, Corda D, Di Girolamo M (2009) Combining affinity purification by ADP-ribose-binding macro domains with mass spectrometry to define the mammalian ADP-ribosyl proteome. Proc Natl Acad Sci U S A 106:4243–4248

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  • Davis RE, Mysore V, Browning JC, Hsieh JC, Lu QA, Katsikis PD (1998) In situ staining for poly(ADP-ribose) polymerase activity using an NAD analogue. J Histochem Cytochem 46:1279–1289

    Article  PubMed  CAS  Google Scholar 

  • Eide B, Gierschik P, Spiegel A (1986) Immunochemical detection of guanine nucleotide binding proteins mono-ADP-ribosylated by bacterial toxins. Biochemistry 25:6711–6715

    Article  PubMed  CAS  Google Scholar 

  • Fedorova M, Frolov A, Hoffmann R (2010) Fragmentation behavior of Amadori-peptides obtained by non-enzymatic glycosylation of lysine residues with ADP-ribose in tandem mass spectrometry. J Mass Spectrom 45:664–669

    PubMed  CAS  Google Scholar 

  • Feijs KL, Verheugd P, Luscher B (2013) Expanding functions of intracellular resident mono-ADP-ribosylation in cell physiology. FEBS J 280:3519–3529

    Article  PubMed  CAS  Google Scholar 

  • Fujimura S, Hasegawa S, Shimizu Y, Sugimura T (1967) Polymerization of the adenosine 5’-diphosphate-ribose moiety of nicotinamide-adenine dinucleotide by nuclear enzyme. I. Enzymatic reactions. Biochim Biophys Acta 145:247–259

    Article  PubMed  CAS  Google Scholar 

  • Ganesan AK, Frank DW, Misra RP, Schmidt G, Barbieri JT (1998) Pseudomonas aeruginosa exoenzyme S ADP-ribosylates Ras at multiple sites. J Biol Chem 273:7332–7337

    Article  PubMed  CAS  Google Scholar 

  • Giovane A, Balestrieri C, Quagliuolo L, Servillo L (1985) 1-N6-Etheno-ADP-ribosylation of elongation factor-2 by diphtheria toxin. FEBS Lett 191:191–194

    Article  PubMed  CAS  Google Scholar 

  • Grahnert A, Friedrich M, Pfister M, Haag F, Koch-Nolte F, Hauschildt S (2002) Mono-ADP-ribosyltransferases in human monocytes: regulation by lipopolysaccharide. Biochem J 362:717–723

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  • He Z, Yang C, Guo G, Li N, Yu W (2011) Motif-All: discovering all phosphorylation motifs. BMC Bioinform 12(Suppl 1):S22

    Article  Google Scholar 

  • Hengel SM, Goodlett DR (2012) A review of tandem mass spectrometry characterization of adenosine diphosphate-ribosylated peptides. Int J Mass Spectrom 312:114–121

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  • Hengel SM, Icenogle L, Collins C, Goodlett DR (2010) Sequence assignment of ADP-ribosylated peptides is facilitated as peptide length increases. Rapid Commun Mass Spectrom 24:2312–2316

    Article  PubMed  CAS  Google Scholar 

  • Hengel SM, Shaffer SA, Nunn BL, Goodlett DR (2009) Tandem mass spectrometry investigation of ADP-ribosylated kemptide. J Am Soc Mass Spectrom 20:477–483

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  • Hingorani VN, Ho YK (1988) Fluorescent labeling of signal-transducing G-proteins. Pertussis toxin-catalyzed etheno-ADP ribosylation of transducin. J Biol Chem 263:19804–19808

    PubMed  CAS  Google Scholar 

  • Honjo T, Nishizuka Y, Hayaishi O (1968) Diphtheria toxin-dependent adenosine diphosphate ribosylation of aminoacyl transferase II and inhibition of protein synthesis. J Biol Chem 243:3553–3555

    PubMed  CAS  Google Scholar 

  • Hottiger MO, Hassa PO, Luscher B, Schuler H, Koch-Nolte F (2010) Toward a unified nomenclature for mammalian ADP-ribosyltransferases. Trends Biochem Sci 35:208–219

    Article  PubMed  CAS  Google Scholar 

  • Karras GI, Kustatscher G, Buhecha HR, Allen MD, Pugieux C, Sait F, Bycroft M, Ladurner AG (2005) The macro domain is an ADP-ribose binding module. EMBO J 24:1911–1920

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  • Klebl BM, Gopel SO, Pette D (1997) Specificity and target proteins of arginine-specific mono-ADP-ribosylation in T-tubules of rabbit skeletal muscle. Arch Biochem Biophys 347:155–162

    Article  PubMed  CAS  Google Scholar 

  • Klebl BM, Pette D (1996) A fluorometric assay for measurement of mono-ADP-ribosyltransferase activity. Anal Biochem 239:145–152

    Article  PubMed  CAS  Google Scholar 

  • Krebs C, Koestner W, Nissen M, Welge V, Parusel I, Malavasi F, Leiter EH, Santella RM, Haag F, Koch-Nolte F (2003) Flow cytometric and immunoblot assays for cell surface ADP-ribosylation using a monoclonal antibody specific for ethenoadenosine. Anal Biochem 314:108–115

    Article  PubMed  CAS  Google Scholar 

  • Laing S, Koch-Nolte F, Haag F, Buck F (2011) Strategies for the identification of arginine ADP-ribosylation sites. J Proteomics 75:169–176

    Article  PubMed  CAS  Google Scholar 

  • Laing S, Unger M, Koch-Nolte F, Haag F (2010) ADP-ribosylation of arginine. Amino Acids 41:257–269

    Article  PubMed  PubMed Central  Google Scholar 

  • Liao SD, Puro DG (2006) NAD+-induced vasotoxicity in the pericyte-containing microvasculature of the rat retina: effect of diabetes. Invest Ophthalmol Vis Sci 47:5032–5038

    Article  PubMed  Google Scholar 

  • Lischke T, Schumacher V, Wesolowski J, Hurwitz R, Haag F, Koch-Nolte F, Mittrucker HW (2013) CD8-beta ADP-ribosylation affects CD8(+) T-cell function. Eur J Immunol 43:1828–1838

    Article  PubMed  CAS  Google Scholar 

  • Liu XC, Scouten WH (2000) Boronate affinity chromatography. Methods Mol Biol 147:119–128

    Article  PubMed  CAS  Google Scholar 

  • Liu XC, Scouten WH (2005) Boronate affinity chromatography. In: Hage DS (ed) Handbook of affinity chromatography. CRC Press, Boca Raton, pp 215–229

    Google Scholar 

  • Lowery RG, Ludden PW (1988) Purification and properties of dinitrogenase reductase ADP-ribosyltransferase from the photosynthetic bacterium Rhodospirillum rubrum. J Biol Chem 263:16714–16719

    PubMed  CAS  Google Scholar 

  • Macek B, Mann M, Olsen JV (2009) Global and site-specific quantitative phosphoproteomics: principles and applications. Annu Rev Pharmacol Toxicol 49:199–221

    Article  PubMed  CAS  Google Scholar 

  • Margarit SM, Davidson W, Frego L, Stebbins CE (2006) A steric antagonism of actin polymerization by a salmonella virulence protein. Structure 14:1219–1229

    Article  PubMed  CAS  Google Scholar 

  • Matic I, Ahel I, Hay RT (2012) Reanalysis of phosphoproteomics data uncovers ADP-ribosylation sites. Nat Methods 9:771–772

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  • Matsubara H, Hasegawa S, Fujimura S, Shima T, Sugimura T (1970) Studies on poly (adenosine diphosphate ribose). V. Mechanism of hydrolysis of poly (adenosine diphosphate ribose) by snake venom phosphodiesterase. J Biol Chem 245:3606–3611

    PubMed  CAS  Google Scholar 

  • McDonald LJ, Moss J (1993) Stimulation by nitric oxide of an NAD linkage to glyceraldehyde-3-phosphate dehydrogenase. Proc Natl Acad Sci U S A 90:6238–6241

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  • McDonald LJ, Moss J (1994) Enzymatic and nonenzymatic ADP-ribosylation of cysteine. Mol Cell Biochem 138:221–226

    Article  PubMed  CAS  Google Scholar 

  • McDonald LJ, Wainschel LA, Oppenheimer NJ, Moss J (1992) Amino acid-specific ADP-ribosylation: structural characterization and chemical differentiation of ADP-ribose-cysteine adducts formed nonenzymatically and in a pertussis toxin-catalyzed reaction. Biochemistry 31:11881–11887

    Article  PubMed  CAS  Google Scholar 

  • Mellacheruvu D, Wright Z, Couzens AL, Lambert JP, St-Denis NA, Li T, Miteva YV, Hauri S, Sardiu ME, Low TY, Halim VA, Bagshaw RD, Hubner NC, Al-Hakim A, Bouchard A, Faubert D, Fermin D, Dunham WH, Goudreault M, Lin ZY, Badillo BG, Pawson T, Durocher D, Coulombe B, Aebersold R, Superti-Furga G, Colinge J, Heck AJ, Choi H, Gstaiger M, Mohammed S, Cristea IM, Bennett KL, Washburn MP, Raught B, Ewing RM, Gingras AC, Nesvizhskii AI (2013) The CRAPome: a contaminant repository for affinity purification-mass spectrometry data. Nat Methods 10:730–736

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  • Meyer T, Hilz H (1986) Production of anti-(ADP-ribose) antibodies with the aid of a dinucleotide-pyrophosphatase-resistant hapten and their application for the detection of mono(ADP-ribosyl)ated polypeptides. Eur J Biochem 155:157–165

    Article  PubMed  CAS  Google Scholar 

  • Meyer T, Koch R, Fanick W, Hilz H (1988) ADP-ribosyl proteins formed by pertussis toxin are specifically cleaved by mercury ions. Biol Chem Hoppe Seyler 369:579–583

    Article  PubMed  CAS  Google Scholar 

  • Moss J, Yost DA, Stanley SJ (1983) Amino acid-specific ADP-ribosylation. J Biol Chem 258:6466–6470

    PubMed  CAS  Google Scholar 

  • Nishizuka Y, Ueda K, Nakazawa K, Hayaishi O (1967) Studies on the polymer of adenosine diphosphate ribose. I. Enzymic formation from nicotinamide adenine dinuclotide in mammalian nuclei. J Biol Chem 242:3164–3171

    PubMed  CAS  Google Scholar 

  • Okayama H, Ueda K, Hayaishi O (1978) Purification of ADP-ribosylated nuclear proteins by covalent chromatography on dihydroxyboryl polyacrylamide beads and their characterization. Proc Natl Acad Sci U S A 75:1111–1115

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  • Osago H, Terashima M, Hara N, Yamada K, Tsuchiya M (2008) A new detection method for arginine-specific ADP-ribosylation of protein – a combinational use of anti-ADP-ribosylarginine antibody and ADP-ribosylarginine hydrolase. J Biochem Biophys Methods 70:1014–1019

    Article  PubMed  CAS  Google Scholar 

  • Osago H, Yamada K, Shibata T, Yoshino K, Hara N, Tsuchiya M (2009) Precursor ion scanning and sequencing of arginine-ADP-ribosylated peptide by mass spectrometry. Anal Biochem 393:248–254

    Article  PubMed  CAS  Google Scholar 

  • Paone G, Stevens LA, Levine RL, Bourgeois C, Steagall WK, Gochuico BR, Moss J (2006) ADP-ribosyltransferase-specific modification of human neutrophil peptide-1. J Biol Chem 281:17054–17060

    Article  PubMed  CAS  Google Scholar 

  • Rosenqvist H, Ye J, Jensen ON (2011) Analytical strategies in mass spectrometry-based phosphoproteomics. Methods Mol Biol 753:183–213

    Article  PubMed  CAS  Google Scholar 

  • Rosenthal F, Messner S, Roschitzki B, Gehrig P, Nanni P, Hottiger MO (2011) Identification of distinct amino acids as ADP-ribose acceptor sites by mass spectrometry. Methods Mol Biol 780:57–66

    Article  PubMed  CAS  Google Scholar 

  • Scheuplein F, Schwarz N, Adriouch S, Krebs C, Bannas P, Rissiek B, Seman M, Haag F, Koch-Nolte F (2009) NAD+ and ATP released from injured cells induce P2X7-dependent shedding of CD62L and externalization of phosphatidylserine by murine T cells. J Immunol 182:2898–2908

    Article  PubMed  CAS  Google Scholar 

  • Schwab CJ, Colville MJ, Fullerton AT, McMahon KK (2000) Evidence of endogenous mono-ADP-ribosylation of cardiac proteins via anti-ADP-ribosylarginine immunoreactivity. Proc Soc Exp Biol Med 223:389–396

    Article  PubMed  CAS  Google Scholar 

  • Seman M, Adriouch S, Haag F, Koch-Nolte F (2004) Ecto-ADP-ribosyltransferases (ARTs): emerging actors in cell communication and signaling. Curr Med Chem 11:857–872

    Article  PubMed  CAS  Google Scholar 

  • Seman M, Adriouch S, Scheuplein F, Krebs C, Freese D, Glowacki G, Deterre P, Haag F, Koch-Nolte F (2003) NAD-induced T cell death: ADP-ribosylation of cell surface proteins by ART2 activates the cytolytic P2X7 purinoceptor. Immunity 19:571–582

    Article  PubMed  CAS  Google Scholar 

  • Takei Y, Takahashi K, Kanaho Y, Katada T (1994) Pertussis toxin-catalyzed ADP-ribosylation of GTP-binding proteins with digoxigenin-conjugated NAD. Identification of the proteins in plasma membranes and nuclei. FEBS Lett 338:264–266

    Article  PubMed  CAS  Google Scholar 

  • Ubersax JA, Ferrell JE Jr (2007) Mechanisms of specificity in protein phosphorylation. Nat Rev Mol Cell Biol 8:530–541

    Article  PubMed  CAS  Google Scholar 

  • Young TL, Santella RM (1988) Development of techniques to monitor for exposure to vinyl chloride: monoclonal antibodies to ethenoadenosine and ethenocytidine. Carcinogenesis 9:589–592

    Article  PubMed  CAS  Google Scholar 

  • Zee BM, Garcia BA (2009) Electron transfer dissociation facilitates sequencing of adenosine diphosphate-ribosylated peptides. Anal Chem 82:28–31

    Article  Google Scholar 

  • Zhang J (1997) Use of biotinylated NAD to label and purify ADP-ribosylated proteins. Methods Enzymol 280:255–265

    Article  PubMed  CAS  Google Scholar 

  • Zhang J, Snyder SH (1993) Purification of a nitric oxide-stimulated ADP-ribosylated protein using biotinylated beta-nicotinamide adenine dinucleotide. Biochemistry 32:2228–2233

    Article  PubMed  CAS  Google Scholar 

  • Zhang Y, Wang J, Ding M, Yu Y (2013) Site-specific characterization of the Asp- and Glu-ADP-ribosylated proteome. Nat Methods 10:981–984

    Article  PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Institute of Immunology, University Medical Center Hamburg-Eppendorf, Martinistr. 52, 20246, Hamburg, Germany

    Friedrich Haag & Friedrich Buck

  2. Institute of Clinical Chemistry, University Medical Center Hamburg-Eppendorf, Martinistr. 52, 20246, Hamburg, Germany

    Friedrich Buck

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  1. Friedrich Haag
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Correspondence to Friedrich Buck .

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Editors and Affiliations

  1. Institute of Immunology, University Medical Center, Hamburg, Germany

    Friedrich Koch-Nolte

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Haag, F., Buck, F. (2014). Identification and Analysis of ADP-Ribosylated Proteins. In: Koch-Nolte, F. (eds) Endogenous ADP-Ribosylation. Current Topics in Microbiology and Immunology, vol 384. Springer, Cham. https://doi.org/10.1007/82_2014_424

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