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Microheterogeneity of Proteins: Role in Diseases

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Biology of C Reactive Protein in Health and Disease

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Abstract

Protein posttranslational modifications largely influence their biological functions. The functions included effect on receptor binding, metabolism of the protein, tissue uptake, degradation, excretion, and protein–protein interactions. Modifications of proteins at and after translation also called as posttranslational modifications or PTM occur at a normal physiological concentration of the protein. However, in some diseases, modifications highly specific to the disease also are known to occur. Thus, disease-specific posttranslational modifications find importance as diagnostic markers in clinical medicine. Different approaches, most of which are analytical to study the posttranslational modifications in protein together their interactions, and their complex structure and function are illustrated by various researchers in immunology, biochemistry, biophysics, and clinical medicine and in proteomics. Immuno assay based affinity purification of protein by HPLC and chromatographic methods, and characterization of proteins by lectin binding assays, biophysical methods like MS or mass spectrometry, and surface-enhanced laser desorption/ionization method find importance as diagnostic techniques in clinical proteomic studies, in the detection of the disease-specific protein modification.

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References

  • Ali S, Bassett JR (1995) Studies on the role of glycosylation in the origin of the electrophoretic variants for rat corticosteroid-binding globulin. Steroids 60(11):743–752

    Article  CAS  PubMed  Google Scholar 

  • Ansar W, Bandyopadhyay SM, Chowdhury S, Habib SH, Mandal C (2006) Role of C-reactive protein in complement mediated hemolysis in Malaria. Glycoconj J 23(3–4):233–240

    Article  CAS  PubMed  Google Scholar 

  • Ansar W, Habib SK, Roy S, Mandal C, Mandal C (2009a) Unraveling the C-reactive protein complement-cascade in destruction of red blood cells: potential pathological implications in Plasmodium falciparum malaria. Cell Physiol Biochem 23(1–3):175–190. doi:10.1159/000204106. Epub 2009 Feb 18

    Article  CAS  PubMed  Google Scholar 

  • Ansar W, Mukhopadhyay S, Habib SK, Basu S, Saha B, Sen AK, Mandal CN, Mandal C (2009b) Disease-associated glycosylated molecular variants of human C-reactive protein activate complement-mediated hemolysis of erythrocytes in tuberculosis and Indian visceral leishmaniasis. Glycoconj J 26(9):1151–69. doi:10.1007/s10719-009-9236-y

    Article  CAS  PubMed  Google Scholar 

  • Armstrong PB, Swarnakar S, Srimal S, Misquith S, Hahn EA, Aimes RT, Quigley JP (1996) A cytolytic function for a sialic acid-binding lectin that is a member of the pentraxin family of proteins. J Biol Chem 271(25):14717–14721

    Article  CAS  PubMed  Google Scholar 

  • Arthur JM (2003) Proteomics. Curr Opin Nephrol Hypertens 12(4):423–430

    Article  CAS  PubMed  Google Scholar 

  • Ballou SP, Lozanski FB, Hodder S, Rzewnicki DL, Mion LC, Sipe JD, Ford AB, Kushner I (1996) Quantitative and qualitative alterations of acute-phase proteins in healthy elderly persons. Age Ageing 25(3):224–230

    Article  CAS  PubMed  Google Scholar 

  • Batanero E, Villalba M, Rodríguez R (1994) Glycosylation site of the major allergen from olive tree pollen. Allergenic implications of the carbohydrate moiety. Mol Immunol 31(1):31–37

    Article  CAS  PubMed  Google Scholar 

  • Baumann M, Meri S (2004) Techniques for studying protein heterogeneity and post-translational modifications. Expert Rev Proteomics 1(2):207–217

    Article  CAS  PubMed  Google Scholar 

  • Beckman L, Beckman G (1967) Individual and organ-specific variations of human acid phosphatase. Biochem Genet 1(2):145–153

    Article  CAS  PubMed  Google Scholar 

  • Burgess RR, Thompson NE (2002) Advances in gentle immunoaffinity chromatography. Curr Opin Biotechnol 13(4):304–308

    Article  CAS  PubMed  Google Scholar 

  • Castagna L, Zarzur J, Filipetti M, Landa C (1996) Isolation and partial characterization of N-acetyl-D-galactosamine-binding lectins from Epiphragmophora trenquelleonis snail. J Biochem 119(2):372–377

    Article  CAS  PubMed  Google Scholar 

  • Clack JW, Juhl M, Rice CA, Li J, Witzmann FA (2003) Proteomic analysis of transducin beta-subunit structural heterogeneity. Electrophoresis 24(19–20):3493–3499

    Article  CAS  PubMed  Google Scholar 

  • Clarke NJ, Crow FW, Younkin S, Naylor S (2001) Analysis of in vivo-derived amyloid-beta polypeptides by on-line two-dimensional chromatography-mass spectrometry. Anal Biochem 298(1):32–39

    Article  CAS  PubMed  Google Scholar 

  • Das T, Sen A, Kempf T, Pramanik SR, Mandal C, Mandal C (2003) Induction of glycosylation in human C-reactive protein under different pathological conditions. Biochem J 373(Pt 2):345–355

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Das T, Mandal C, Mandal C (2004a) Variations in binding characteristics of glycosylated human C-reactive proteins in different pathological conditions. Glycoconj J 20(9):537–543

    Article  CAS  PubMed  Google Scholar 

  • Das T, Mandal C, Mandal C (2004b) Protein A-a new ligand for human C-reactive protein. FEBS Lett 576:107–113

    Article  CAS  PubMed  Google Scholar 

  • Davies H, Lomas L, Austen B (1999) Profiling of amyloid beta peptide variants using SELDI Protein Chip arrays. Biotechniques 27(6):1258–1261

    CAS  PubMed  Google Scholar 

  • Davis BG (2004) Biochemistry. Mimicking posttranslational modifications of proteins. Science 303(5657):480–482

    Article  CAS  PubMed  Google Scholar 

  • Figeys D (2004) Combining different ‘omics’ technologies to map and validate protein-protein interactions in humans. Brief Funct Genomic Proteomic 2(4):357–365

    Article  CAS  PubMed  Google Scholar 

  • Figeys D, McBroom LD, Moran MF (2001) Mass spectrometry for the study of protein-protein interactions. Methods 24(3):230–239

    Article  CAS  PubMed  Google Scholar 

  • Gericke B, Raila J, Sehouli J, Haebel S, Könsgen D, Mustea A, Schweigert FJ (2005) Microheterogeneity of transthyretin in serum and ascitic fluid of ovarian cancer patients. BMC Cancer 5:133

    Article  PubMed  PubMed Central  Google Scholar 

  • Gerlach D, Wagner M, Schlott B, Zähringer U, Schmidt KH (2002) Chemical and physicochemical characterization of the sialic acid-specific lectin from Cepaea hortensis. FEMS Microbiol Lett 214(1):61–68

    Article  CAS  PubMed  Google Scholar 

  • Goodarzi MT, Turner GA (1996) A lectin-binding assay for the rapid characterization of the glycosylation of purified glycoproteins. In: Walker JM (ed) The protein protocol handbooks. Humana Press, Totowa. doi:10.1007/978-1-60327-259-9_98

    Google Scholar 

  • Grant SG, Husi H (2001) Proteomics of multiprotein complexes: answering fundamental questions in neuroscience. Trends Biotechnol 19(10 Suppl):S49–S54

    Article  CAS  PubMed  Google Scholar 

  • Grzymisławski M, Derc K, Sobieska M, Wiktorowicz K (2006) Microheterogeneity of acute phase proteins in patients with ulcerative colitis. World J Gastroenterol 12(32):5191–5195

    PubMed  PubMed Central  Google Scholar 

  • Hage DS (1999) Affinity chromatography: a review of clinical applications. Clin Chem 45(5):593–615

    CAS  PubMed  Google Scholar 

  • Hanash S (2003) Disease proteomics. Nature 422(6928):226–232

    Article  CAS  PubMed  Google Scholar 

  • Hancock WS (2002) Glycosylation, who cares? J Proteome Res 1(4):297

    Article  CAS  PubMed  Google Scholar 

  • Hansen JE, Larsen VA, Bøg-Hansen TC (1984) The microheterogeneity of alpha 1-acid glycoprotein in inflammatory lung disease, cancer of the lung and normal health. Clin Chim Acta 138(1):41–47

    Article  CAS  PubMed  Google Scholar 

  • Hansen JE, Iversen J, Lihme A, Bøg-Hansen TC (1987) Acute phase reaction, heterogeneity, and microheterogeneity of serum proteins as nonspecific tumor markers inlung cancer. Cancer 60(7):1630–1635

    Article  CAS  PubMed  Google Scholar 

  • Havenaar EC, Drenth JP, van Ommen EC, van der Meer JW, van Dijk W (1995) Elevated serum level and altered glycosylation of alpha 1- acid glycoprotein in hyperimmunoglobulinemia D and periodic fever syndrome: evidence for persistent inflammation. Clin Immunol Immunopathol 76(3 Pt 1):279–284

    Article  CAS  PubMed  Google Scholar 

  • Haynes P, Miller I, Aebersold R, Gemeiner M, Eberini I, Lovati MR, Manzoni C, Vignati M, Gianazza E (1998) Proteins of rat serum: I. Establishing a reference two-dimensional electrophoresis map by immunodetection and microbore high performance liquid chromatography-electrospray mass spectrometry. Electrophoresis 19(8–9):1484–1492

    Article  CAS  PubMed  Google Scholar 

  • Hochstrasser DF, Sanchez JC, Appel RD (2002) Proteomics and its trends facing nature’s complexity. Proteomics 2(7):807–812

    Article  CAS  PubMed  Google Scholar 

  • Hrycaj P, Sobieska M, Mackiewicz S, Müller W (1993) Microheterogeneity of alpha 1 acid glycoprotein in rheumatoid arthritis: dependent on disease duration? Ann Rheum Dis 52(2):138–141

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hrycaj P, Wurm K, Mennet P, Müller W (1996) Microheterogeneity of acute-phase glycoproteins in patients with pulmonary sarcoidosis. Eur Respir J 9(2):313–318

    Article  CAS  PubMed  Google Scholar 

  • Iijima S, Shiba K, Kimura M, Nagai K, Iwai T (2000) Changes of alpha1-acid glycoprotein microheterogeneity in acute inflammation stages analyzed by isoelectricfocusing using serum obtained postoperatively. Electrophoresis 21(4):753–759

    Article  CAS  PubMed  Google Scholar 

  • Iwaki D, Osaki T, Mizunoe Y, Wai SN, Iwanaga S, S K (1999) Functional and structural diversities of C-reactive proteins present in horseshoe crab hemolymph plasma. Eur J Biochem 264(2):314–326

    Article  CAS  PubMed  Google Scholar 

  • Kiernan UA, Tubbs KA, Nedelkov D, Niederkofler EE, McConnell E, Nelson RW (2003) Comparative urine protein phenotyping using mass spectrometric immunoassay. J Proteome Res 2(2):191–197

    Article  CAS  PubMed  Google Scholar 

  • Kushner I (1982) The phenomenon of the acute phase response. Ann N Y Acad Sci 389:39–48

    Article  CAS  PubMed  Google Scholar 

  • Kushner I, Mackiewicz A (1987) Acute phase proteins as disease markers. Dis Markers 5(1):1–11

    CAS  PubMed  Google Scholar 

  • Lal SP, Christopherson RI, dos Remedios CG (2002) Antibody arrays: an embryonic but rapidly growing technology. Drug Discov Today 7(18 Suppl):S143–S149

    Article  CAS  PubMed  Google Scholar 

  • Lasson A, Göransson J (1999) No microheterogenous changes of plasma C-reactive protein found in man during various diseases. Scand J Clin Lab Invest 59(4):293–304

    Article  CAS  PubMed  Google Scholar 

  • Li P, Mold C, Du Clos TW (1994) Sublytic complement attack exposes C-reactive protein binding sites on cell membranes. J Immunol 152(6):2995–3005

    CAS  PubMed  Google Scholar 

  • Lim A, Sengupta S, McComb ME, Théberge R, Wilson WG, Costello CE, Jacobsen DW (2003) In vitro and in vivo interactions of homocysteine with human plasma transthyretin. J Biol Chem 278(50):49707–49713. Epub 2003 Sep 24

    Article  CAS  PubMed  Google Scholar 

  • Lin Z, Crockett DK, Lim MS, Elenitoba-Johnson KS (2003) High-throughput analysis of protein/peptide complexes by immunoprecipitation and automated LC-MS/MS. J Biomol Tech 14(2):149–155

    PubMed  PubMed Central  Google Scholar 

  • Mackiewicz A, Pawłowski T, Mackiewicz-Pawłowska A, Wiktorowicz K, Mackiewicz S (1987a) Microheterogeneity forms of alpha 1-acid glycoprotein as indicators of rheumatoid arthritis activity. Clin Chim Acta 163(2):185–190

    Article  CAS  PubMed  Google Scholar 

  • Mackiewicz A, Marcinkowska-Pieta R, Ballou S, Mackiewicz S, Kushner I (1987b) Microheterogeneity of alpha 1-acid glycoprotein in the detection of intercurrent infection in systemic lupus erythematosus. Arthritis Rheum 30(5):513–518

    Article  CAS  PubMed  Google Scholar 

  • Mackiewicz A, Khan MA, Reynolds TL, van der Linden S, Kushner I (1989) Serum IgA, acute phase proteins, and glycosylation of alpha 1-acid glycoprotein in ankylosing spondylitis. Ann Rheum Dis 48(2):99–103

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Mandal C, Sinha S, Mandal C (1999) Lectin like properties and differential sugar binding characteristics of C-reactive proteins purified from sera of normal and pollutant induced Labeo rohita. Glycoconj J 16(11):741–750

    Article  CAS  PubMed  Google Scholar 

  • Mandal C, Srinivasan GV, Chowdhury S, Chandra S, Mandal C, Schauer R, Mandal C (2009) High level of sialate-O-acetyltransferase activity in lymphoblasts of childhood acute lymphoblastic leukaemia(ALL): enzyme characterization and correlation with disease status. Glycoconj J 26(1):57–73. doi:10.1007/s10719-008-9163-3. Epub 2008 Aug 3

    Article  CAS  PubMed  Google Scholar 

  • Mann M, Jensen ON (2003) Proteomic analysis of post-translational modifications. Nat Biotechnol 21(3):255–261

    Article  CAS  PubMed  Google Scholar 

  • Maudsley S, Rowe IF, de Beer FC, Munn EA, Herbert J, Feinstein A, Pepys MB (1987) Identification and isolation of two pentraxins from bovine serum. Clin Exp Immunol 67(3):662–673

    CAS  PubMed  PubMed Central  Google Scholar 

  • Molloy MP, Witzmann FA (2002) Proteomics: technologies and applications. Brief Funct Genomic Proteomic 1(1):23–39

    Article  CAS  PubMed  Google Scholar 

  • Morley JJ, Kushner I (1982) Serum C-reactive protein levels in disease. Ann N Y Acad Sci 389:406–418

    Article  CAS  PubMed  Google Scholar 

  • Morris HR, Chatterjee A, Panico M, Green BN, Almeida da Silva MA, Hartley BS (1989) Linked scans of peptides and protein digests: amino acid sequence determination of components of complex mixtures. Rapid Commun Mass Spectrom 3(4):110–116

    Article  CAS  PubMed  Google Scholar 

  • Nair KS, Jaleel A, Asmann YW, Short KR, Raghavakaimal S (2004) Proteomic research: potential opportunities for clinical and physiological investigators. Am J Physiol Endocrinol Metab 286(6):E863–E874

    Article  CAS  PubMed  Google Scholar 

  • Nedelkov D, Tubbs KA, Niederkofler EE, Kiernan UA, Nelson RW (2004) High-throughput comprehensive analysis of human plasma proteins: a step toward population proteomics. Anal Chem 76(6):1733–1737

    Article  CAS  PubMed  Google Scholar 

  • Nelson RW, Nedelkov D, Tubbs KA (2000a) Biosensor chip mass spectrometry: a chip-based proteomics approach. Electrophoresis 21(6):1155–1163

    Article  CAS  PubMed  Google Scholar 

  • Nelson RW, Nedelkov D, Tubbs KA (2000b) Biomolecular interaction analysis mass spectometry. BIA/MS can detect and characterize proteins in complex biological fluids at the low- to subfemtomole level. Anal Chem 72(11):404A–411A

    Article  CAS  PubMed  Google Scholar 

  • Packer NH, Harrison MJ (1998) Glycobiology and proteomics: is mass spectrometry the Holy Grail? Electrophoresis 19(11):1872–1882

    Article  CAS  PubMed  Google Scholar 

  • Paul I, Mandal C, Mandal C (1998) Effect of environmental pollutants on the C-reactive protein of a freshwater major carp, Catla catla. Dev Comp Immunol 22(5–6):519–532

    Article  CAS  PubMed  Google Scholar 

  • Paul I, Mandal C, Allen AK, Mandal C (2001) Glycosylated molecular variants of C-reactive proteins from the major carp Catla catla in fresh and polluted aquatic environments. Glycoconj J 18(7):547–556

    Article  CAS  PubMed  Google Scholar 

  • Pawłowski T, Mackiewicz A, Mackiewicz S (1986) Studies on microheterogeneity of acute-phase proteins in rheumatoid arthritis by using crossed affinoimmuno-electrophoresis with free concanavalin A. Behring Inst Mitt 80:11–15

    PubMed  Google Scholar 

  • Pepys MB, Baltz ML (1983) Acute phase proteins with special reference to C-reactive protein and related proteins (pentaxins) and serum amyloid A protein. Adv Immunol 34:141–212

    Article  CAS  PubMed  Google Scholar 

  • Pos O, Oostendorp RA, van der Stelt ME, Scheper RJ, Van Dijk W (1990) Con A-nonreactive human alpha 1-acid glycoprotein (AGP) is more effective in modulation of lymphocyte proliferation than Con A-reactive AGP serum variants. Inflammation 14(2):133–141

    Article  CAS  PubMed  Google Scholar 

  • Potempa LA, Maldonado BA, Laurent P, Zemel ES, Gewurz H (1983) Antigenic, electrophoretic and binding alterations of human C-reactive protein modified selectively in the absence of calcium. Mol Immunol 20(11):1165–1175

    Article  CAS  PubMed  Google Scholar 

  • Raynes J (1982) Variations in the relative proportions of microheterogeneous forms of plasma glycoproteins in pregnancy and disease. Biomed Pharmacother 36(2):77–86

    CAS  PubMed  Google Scholar 

  • Russell RB, Alber F, Aloy P, Davis FP, Korkin D, Pichaud M, Topf M, Sali A (2004) A structural perspective on protein-protein interactions. Curr Opin Struct Biol 14(3):313–324

    Article  CAS  PubMed  Google Scholar 

  • Schweigert FJ (2005) Characterisation of protein microheterogeneity and protein complexes using on-chip immunoaffinity purification-mass spectrometry. Brief Funct Genomic Proteomic 4(1):7–15

    Article  CAS  PubMed  Google Scholar 

  • Shukla AK, Schauer R (1982) Fluorimetric determination of unsubstituted and 9(8)-O-acetylated sialic acids in erythrocyte membranes. Hoppe Seylers Z Physiol Chem 363(3):255–262

    Article  CAS  PubMed  Google Scholar 

  • Sinha S, Mandal C (1996) Microheterogeneity of C-reactive protein in the sera of fish Labeo rohita induced by metal pollutants. Biochem Biophys Res Commun 226(3):681–687

    Article  CAS  PubMed  Google Scholar 

  • Sinha S, Mandal C, Allen AK, Mandal C (2001) Acute phase response of C-reactive protein of Labeo rohita to aquatic pollutants is accompanied by the appearance of distinct molecular forms. Arch Biochem Biophys 396(2):139–150

    Article  CAS  PubMed  Google Scholar 

  • Sloneker JH (1972) Gas–liquid chromatography of alditol acetates. In: Whistler RL, BeMiller JN (eds) Methods in carbohydrate chemistry, VI edn. Academic Press Inc., New York, pp 20–24.

    Google Scholar 

  • Smith JK, Whitby LG (1968) The heterogeneity of prostatic acid phosphatase. Biochim Biophys Acta 151(3):607–618

    Article  CAS  PubMed  Google Scholar 

  • Spiro RC, Parsons WG, Perry SK, Caulfield JP, Hein A, Reisfeld RA, Harper JR, Austen KF, Stevens RL (1986) Inhibition of post-translational modification and surface expression of a melanoma-associated chondroitin sulfate proteoglycan by diethylcarbamazine or ammonium chloride. J Biol Chem 261(11):5121–5129

    CAS  PubMed  Google Scholar 

  • Srinivasan N, White HE, Emsley J, Wood SP, Pepys MB, Blundell TL (1994) Comparative analyses of pentraxins: Implications for protomer assembly and ligand binding. Structure 2(11):1017–1027

    Article  CAS  PubMed  Google Scholar 

  • Sydor JR, Scalf M, Sideris S, Mao GD, Pandey Y, Tan M, Mariano M, Moran MF, Nock S, Wagner P (2003) Chip-based analysis of protein-protein interactions by fluorescence detection and on-chip immunoprecipitation combined with microLC-MS/MS analysis. Anal Chem 75(22):6163–6170

    Article  CAS  PubMed  Google Scholar 

  • Szalai AJ, Norcum MT, Bly JE, Clem LW (1992) Isolation of an acute-phase phosphorylcholine-reactive pentraxin from channel catfish (Ictalurus punctatus). Comp Biochem Physiol B 102(3):535–543

    CAS  PubMed  Google Scholar 

  • Tillett WS, Francis T (1930) Serological reactions in pneumonia with a non-protein somatic fraction of pneumococcus. J Exp Med 52(4):561–571

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Tolson J, Bogumil R, Brunst E, Beck H, Elsner R, Humeny A, Kratzin H, Deeg M, Kuczyk M, Mueller GA, Mueller CA, Flad T (2004) Serum protein profiling by SELDI mass spectrometry: detection of multiple variants of serum amyloid alpha in renal cancer patients. Lab Invest 84(7):845–856

    Article  CAS  PubMed  Google Scholar 

  • Tubbs KA, Nedelkov D, Nelson RW (2001) Detection and quantification of beta-2-microglobulin using mass spectrometric immunoassay. Anal Biochem 289(1):26–35

    Article  CAS  PubMed  Google Scholar 

  • Tyers M, Mann M (2003) From genomics to proteomics. Nature 422(6928):193–197

    Article  CAS  PubMed  Google Scholar 

  • Wang HW, Wu Y, Chen Y, Sui SF (2002) Polymorphism of structural forms of C-reactive protein. Int J Mol Med 9(6):665–671

    CAS  PubMed  Google Scholar 

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  1. Department of Zoology, Behala College, Kolkata, West Bengal, India

    Waliza Ansar

  2. National Institute of Science Education, School of Biological Sciences, Bhubaneswar, Odisha, India

    Shyamasree Ghosh

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  1. Waliza Ansar
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Ansar, W., Ghosh, S. (2016). Microheterogeneity of Proteins: Role in Diseases. In: Biology of C Reactive Protein in Health and Disease. Springer, New Delhi. https://doi.org/10.1007/978-81-322-2680-2_5

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