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Thromb Haemost 2000; 84(06): 1057-1065
DOI: 10.1055/s-0037-1614171
Review Article
Schattauer GmbH

Identification of a Putative Binding Site for Negatively Charged Surfaces in the Fibronectin Type II Domain of Human Factor XII

An Immunochemical and Homology Modeling Approach
Franca Citarella
1   From CLB Sanquin Blood Supply Foundation, Department of Pathophysiology of Plasma Proteins and Laboratory for Experimental and Clinical Immunology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands
2   Dipartimento di Biotecnologie Cellulari ed Ematologia, Sezione di Genetica Molecolare, Università di Roma “La Sapienza”, Roma, Italy
,
Henk te Velthuis
1   From CLB Sanquin Blood Supply Foundation, Department of Pathophysiology of Plasma Proteins and Laboratory for Experimental and Clinical Immunology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands
,
Manuela Helmer-Citterich
3   I.N.F.M and Dipartimento di Biologia, Università di Roma Tor Vergata, Italy
,
C. Erik Hack
1   From CLB Sanquin Blood Supply Foundation, Department of Pathophysiology of Plasma Proteins and Laboratory for Experimental and Clinical Immunology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands
4   Department of Clinical Chemistry, Academic Hospital, “Vrije Universiteit”, Amsterdam, The Netherlands
› InstitutsangabenWe thank Dorina Roem for the excellent technical support. We are grateful to Prof. Rob Aalberse for valuable discussions and to Prof. Lucien Aarden for critical reading of the manuscript.
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Publikationsverlauf

Received 17. Dezember 1999

Accepted after resubmission 18. Juli 2000

Publikationsdatum:
13. Dezember 2017 (online)

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Summary

Monoclonal antibodies directed against functional sites of proteins provide useful tools for structure-function studies. Here we describe a mAb, KOK5, directed against the heavy chain region of human coagulation factor XII (FXII), which inhibits kaolin-induced clotting activity by preventing the binding of FXII to kaolin. Furthermore, mAb KOK5 enhances FXII susceptibility for cleavage by kallikrein and supports FXII autoactivation. Hence, mAb KOK5 likely is directed against the binding site of FXII for negatively charged surfaces. Screening of two phage-displayed random peptide libraries with mAb KOK5 selected phages that could be grouped on the basis of two amino acid consensus sequences: A) FXFQTPXW and B) HQ/LCTHR/KKC. Sequence A contains two motifs: one shares homology with FXII amino acid residues 30-33 (FPFQ), the second one with residues 57-60 (TPNF); both amino acid stretches belonging to the fibronectin type II domain of FXII. Sequence B also reveals homology with part of the fibronectin type II domain, i.e. the stretch 40-47 (HKCTHKGR). A three-dimensional model of FXII residues 28-65, obtained by homology modeling, indicated that the three amino acid stretches 30-33, 40-47 and 57-60 are close to each other and accessible for the solvent, i.e. in a form available for interaction with the monoclonal antibody, suggesting that mAb KOK5 recognizes a discontinuous epitope on the fibronectin type II domain of FXII. Peptides corresponding to FXII sequences 29-37 (FXII29-37) or 39-47 (FXII39-47), were synthesized and tested for the capability to inhibit FXII binding to negatively charged surfaces. Peptide FXII39-47 inhibited the binding of labeled FXII to kaolin and effectively prevented both dextran sulfate-and kaolin-induced activation of the contact system in plasma. Hence, we suggest that the fibronectin type II domain of FXII, in particular residues 39 to 47, contribute to the binding site of FXII for negatively charged surfaces.

Key words

Factor XII - binding site - fibronectin type II
 

  • References

  • 1 Cochrane CG, Griffin JH. The biochemistry and pathophysiology of the contact system of plasma. Adv Immunol 1982; 33: 241-304.
    PubMedSuche in Google Scholar
  • 2 Colman RW. Surface-mediated defense reactions. The plasma contact activation system. J Clin Invest 1984; 73: 1249-53.
    CrossrefPubMedSuche in Google Scholar
  • 3 Griffin JH, Bouma BN. The contact phase of blood coagulation. In Haemostasis and thrombosis. Bloom AL, Thomas DP. eds. Edinburgh, Churchill Livingstone; 1987: 101-15.
    Suche in Google Scholar
  • 4 Kaplan AP, Silverberg M. The coagulation?kinin pathway of human plasma. Blood 1987; 70: 1-15.
    PubMedSuche in Google Scholar
  • 5 Levi M, Hack CE, De Boer JP, Brandjes DPM, Büller HR, ten Kate WJ. Reduction of contact activation related fibrinolytic activity in factor XII deficient patients. Further evidence for the role of the contact system in fibrinolysis in vivo. J Clin Invest 1991; 88: 1155-60.
    CrossrefPubMedSuche in Google Scholar
  • 6 Jansen PM, Pixley RA, Brouwer M, de Jong IW, Chang AC, Hack CE, Taylor Jr FB, Colman RW. Inhibition of factor XII in septic baboons attenuates activation of complement nand fibrinolytic system and reduces the release of interleukin-6 and neutrophil elastase. Blood 1996; 87: 2337-44.
    PubMedSuche in Google Scholar
  • 7 Wachtfogel YT, DeLa Cadena RA, Colman RW. Structural Biology, Cellular Interactions and Pathophysiology of the Contact System. Thromb Res 1993; 72: 1-21.
    CrossrefPubMedSuche in Google Scholar
  • 8 Colman RW, Schmaier AH. Contact System: A vascular biology modulator with anticoagulant, profibrinolytic, antiadhesive, and proinflammatory attributes. Blood 1997; 90: 3819-43.
    PubMedSuche in Google Scholar
  • 9 Cool DE, Edgell CS, Louie GV, Zoller MJ, Brayer GD, Macgillivray RTA. Characterization of human blood coagulation Factor XII cDNA. Prediction of the primary structure of Factor XII and the tertiary structure of betaFactor XIIa. J Biol Chem 1985; 260: 13666-76.
    PubMedSuche in Google Scholar
  • 10 Cool DE, Macgillivray RTA. Characterization of the human blood coagulation factor XII gene. J Biol Chem 1987; 262: 13662-73.
    CrossrefPubMedSuche in Google Scholar
  • 11 Pixley RA, Colman RW. Factor XII; Hageman Factor. In: Proteolytic Enzymes in Coagulation, Fibrinolysis, and Complement Activation. Lorand L, Mann KG. eds. San Diego: Academic Press, Inc; 1993: 51-65.
    Suche in Google Scholar
  • 12 Reddigari SR, Shibayama Y, Brunee T, Kaplan AP. Human Hageman factor (factor XII0 and high molecular weight kininogen compete for the same binding site on human umbilical vein endothelial cells. J Biol Chem 1993; 286: 11982-7.
    PubMedSuche in Google Scholar
  • 13 Henderson LM, Figueroa CD, Muller-Ester Bhoola KD. Assembly of contact-phase factors on the surface of the human neutrophil membrane. Blood 1994; 84: 474-82.
    PubMedSuche in Google Scholar
  • 14 Cochrane CG, Revak SD, Wuepper KD. Activation of Hageman factor in solid and fluid phases. J Exp Med 1973; 138: 1564-1583.
    CrossrefPubMedSuche in Google Scholar
  • 15 Griffin JH. Role of surface in surface-dependent activation of Hageman factor (blood coagulation Factor XII). Proc Nat Acad Sci USA 1978; 75: 1998-2002.
    CrossrefPubMedSuche in Google Scholar
  • 16 Samuel M, Pixley RA, Villanueva MA, Colman RW, Villanueva GB. Human Factor XII (Hageman Factor) Autoactivation by Dextran Sulfate Circular Dichroism, Fluorescence, and Ultraviolet Difference Spectroscopic Studies. J Biol Chem 1992; 267: 19691-7.
    CrossrefPubMedSuche in Google Scholar
  • 17 Dunn JT, Silverberg M, Kaplan AP. The cleavage and formation of activated human Hageman factor by autodigestion and by kallikrein. J Biol Chem 1982; 257: 1779-84.
    PubMedSuche in Google Scholar
  • 18 Tankersley DL, Finlayson JS. Kinetics of activation and autoactivation of human factor XII. Biochemistry 1984; 23: 273-9.
    CrossrefPubMedSuche in Google Scholar
  • 19 Citarella F, Willemin WA, Lubbers YTP, Hack CE. Initiation of contact system activation in plasma is dependent on factor XII autoactivation and not on enhanced susceptibility of factor XII for kallikrein cleavage. Br J Haemat 1997; 99: 197-205.
    CrossrefPubMedSuche in Google Scholar
  • 20 Lawson JH, Kalafatis M, Stram S, Mann KG. A model for the Tissue Factor pathway to Thrombin. J Biol Chem 1994; 269: 23357-66.
    PubMedSuche in Google Scholar
  • 21 Revak SD, Cochrane CG, Griffin JH. The binding and cleavage characteristics of human Hageman factor during contact activation. A comparison of normal plasma with plasmas deficient in factor XI, prekallikrein, or high molecular weight kininogen. J Clin Invest 1977; 59: 1167-75.
    CrossrefPubMedSuche in Google Scholar
  • 22 Lewin MF, Kaplan AP, Harpel PC. Studies of C1 inactivator-plasma kallikrein complexes in purified systems and in plasma. Quantification by an enzyme-linked differential antibody immunosorbent assay. J Biol Chem 1983; 258: 6415-21.
    PubMedSuche in Google Scholar
  • 23 van der Graaf F, Keus FJA, Vlooswijk RAA, Bouma BN. The contact activation mechanism in human plasma: activation induced by dextran sulfate. Blood 1982; 59: 1225-33.
    PubMedSuche in Google Scholar
  • 24 Bock PE, Srinivasan KR, Shore JD. Activation of intrinsic blood coagulation by ellagic acid: insoluble ellagic acid-metal ion complexes are the activating species. Biochemistry 1981; 20: 7258-66.
    CrossrefPubMedSuche in Google Scholar
  • 25 Pixley RA, Stumpo LG, Birkmeyer K, Silver L, Colman RW. A Monoclonal Antibody Recognizing an Icosapeptide Sequence in the Heavy Chain of Human Factor XII Inhibits Surface-Catalyzed Activation. J Biol Chem 1987; 262: 10140-5.
    CrossrefPubMedSuche in Google Scholar
  • 26 Clarke BJ, Côte HCF, Cool DE, Clark-Lewis I, Saito H, Pixley RA, Colman RW, Macgillivray RTA. Mapping of a putative surface-binding site of human coagulation factor XII. J Biol Chem 1989; 264: 11497-502.
    PubMedSuche in Google Scholar
  • 27 Samuel E, Samuel M, Villanueva GB. Anticoagulant Property and Conformational Flexibility of factor XII-derived peptides. Thromb Haemost 1993; 69: 1306.
    PubMedSuche in Google Scholar
  • 28 Citarella F, Fedele G, Roem D, Fantoni A, Hack CE. The Second Exon-Encoded Factor XII Region Is Involved in the Interaction of Factor XII With Factor XI and Does Not Contribute to the Binding Site of Factor XII for Negatively Charged Surfaces. Blood 1998; 92: 4198-206.
    CrossrefPubMedSuche in Google Scholar
  • 29 Nuijens JH, Huijbregts CCM, Eerenberg-Belmer AJM, Meijers JCM, Bouma BN, Hack CE. Activation of the contact system of coagulation by a monoclonal antibody directed against a neodeterminant in the heavy chain region of human coagulation factor XII (Hageman Factor). J Biol Chem 1989; 264: 12941-9.
    PubMedSuche in Google Scholar
  • 30 Ravon DM, Citarella F, Lubbers YTP, Pascucci B, Hack CE. Monoclonal antibody F1 binds to the kringle domain of factor XII and induces enhanced susceptibility for cleavage by kallikrein. Blood 1995; 11: 4134-43.
    PubMedSuche in Google Scholar
  • 31 Nuijens JH, Huijbregts CCM, Eerenberg AJM, Abbink JJ, Strack van Schijndel RJM, Felt-Bersma RJF, Thijs LG, Hack CE. Quantification of plasma factor XIIa-C1-Inhibitor and kallikrein-C1-Inhibitor complexes in sepsis. Blood 1988; 72: 1841-8.
    PubMedSuche in Google Scholar
  • 32 Citarella F, Ravon DM, Pascucci B, Felici A, Fantoni A, Hack CE. Structure/function analysis of human factor XII using recombinant deletion mutants. Eur J Biochem 1996; 238: 240-9.
    CrossrefPubMedSuche in Google Scholar
  • 33 Wuillemin WA, Minnema M, Meijers JCM, Roem D, Eerenberg AJM, Nuijens JH, ten Cate H, Hack CE. Inactivation of Factor XIa in Human Plasma Assessed by Measuring Factor XIa-Protease Inhibitor Complexes: Major Role for C1-Inhibitor. Blood 1995; 85: 1517-26.
    PubMedSuche in Google Scholar
  • 34 Devlin JJ, Panganiban LC, Devlin PE. Random peptide libraries: a source of specific protein binding molecules. Science 1990; 249: 404-6.
    CrossrefPubMedSuche in Google Scholar
  • 35 Felici F, Castagnoli L, Musacchio A, Jappelli R, Cesareni G. Selection of antibody ligands from a large library of oligopeptides expressed on a multivalent exposition vector. J Mol Biol 1991; 222: 301-10.
    CrossrefPubMedSuche in Google Scholar
  • 36 Luzzago A, Felici F, Tramontano A, Pessi A, Cortese R. Mimicking of discontinuous epitopes by phage-displayed peptides. I. Epitope mapping of human H ferritin using a phage library of constrained peptides. Gene 1993; 128: 51-7.
    CrossrefPubMedSuche in Google Scholar
  • 37 Zonneveld J-A, van den Berg BMM, van Meijer M, Pannekoek H. Identification of functional interaction sites on protein using bacteriophagedisplayed random epitope libraries. Gene 1995; 167: 49-52.
    CrossrefPubMedSuche in Google Scholar
  • 38 Ottenhoff TH, Geluk A, Toebes M, Benckhuijsen WE, Meijgaarden KE, Drijfhout JW. A sensitive fluorometric assay for quantitatively measuring specific peptide binding to HLA class I and class II molecules. J Immunol Methods 1997; 200: 89-97.
    CrossrefPubMedSuche in Google Scholar
  • 39 Sinha D, Koshy A, Seaman FS, Walsh PN. Functional characterization of human coagulation factor XIa using hybridoma antibodies. J Biol Chem 1985; 260: 10714-9.
    PubMedSuche in Google Scholar
  • 40 Schapira M, Scott CF, Colman RW. Contribution of plasma protease inhibitors to the inactivation of kallikrein in plasma. J Clin Invest 1982; 69: 462-8.
    CrossrefPubMedSuche in Google Scholar
  • 41 Pixley RA, Schapira M, Colman RW. The regulation of human factor XIIa by plasma proteinase inhibitors. J Biol Chem 1985; 260: 1723-9.
    PubMedSuche in Google Scholar
  • 42 Kaplan AP, Gruber B, Harpel PC. Assessment of Hageman factor activation in human plasma: quantification of activated Hageman factor-C1 inactivator complexes by an enzyme-linked differential antibody immunosorbent assay. Blood 1985; 66: 636-41.
    PubMedSuche in Google Scholar
  • 43 Nuijens JH, Huijbregts CCM, Cohen M, Navis GO, de Vries A, Eerenberg AJM, Bakker JC, Hack CE. Detection of activation of the contact system of coagulation in vitro and in vivo: quantitation of activated Hageman factor-C1-Inhibitor and kallikrein-C1-Inhibitor complexes by specific radioimmunoassays. Thromb Haemost 1987; 58: 778-85.
    Thieme ConnectPubMedSuche in Google Scholar
  • 44 Kurachi K, Fujikawa K, Davie EW. Mechanism of activation of bovine factor XI by factor XII and factor XIIa. Biochemistry 1980; 19: 1330-8.
    CrossrefPubMedSuche in Google Scholar
  • 45 Friguet B, Chaffotte AF, Djavadi-Ohaniance L, Goldberg ME. Measurements of the true affinity constant in solution of antigen-antibody complexes by enzyme-linked immunoassorbent assay. J Immunol Methods 1985; 77: 305-19.
    CrossrefPubMedSuche in Google Scholar
  • 46 Constantine KL, Ramesh V, Banyai L, Trexler M, Patthy L, Llinas M. Sequence-specific 1 H NMR assignments and structural characterization of bovine seminal fluid protein PDC-109 domain b. Biochemistry 1991; 30: 1663-72.
    CrossrefPubMedSuche in Google Scholar
  • 47 Berger C, Weber-Bornhauser S, Eggenberger J, Hanes J, Plückthun A, Bosshard HR. Antigen recognition by conformational selection. FEBS 1999; 450: 149-53.
    CrossrefPubMedSuche in Google Scholar
  • 48 Stephen CW, Helminen P, Lane DP. Characterization of epitopes on human p53 using phage-displayed peptide libraries: insights into antibody-peptide interactions. J Mol Biol 1995; 248: 58-78.
    CrossrefPubMedSuche in Google Scholar
  • 49 Geysen HM, Rodda SJ, Mason TJ. A priori delineation of a peptide which mimics a discontinuous antigenic determinant. Mol Immunol 1986; 23: 709-15.
    CrossrefPubMedSuche in Google Scholar
  • 50 Geysen HM, Rodda SJ, Mason TJ, Tribbick G, Schoofs PG. Strategies for epitope analysis using peptide synthesis. J Immunol Methods 1987; 102: 259-74.
    CrossrefPubMedSuche in Google Scholar
  • 51 Prezzi C, Nuzzo M, Meola A, Delmastro P, Galfrè G, Cortese R, Nicosia A, Monaci P. Selection of antigenic and immunogenic mimics of hepatitis C virus using sera from patients. J Immunol 1996; 156: 4504-13.
    PubMedSuche in Google Scholar
  • 52 Laver WG, Gillian MA, Webster RG, Smith-Gill SJ. Epitopes on Protein Antigens: Misconceptions and Realities. Cell 1990; 61: 553-6.
    CrossrefPubMedSuche in Google Scholar
  • 53 Luzzago A, Arosio P, Iacobello C, Ruggeri G, Capucci L, Brocchi E, De Simone F, Gamba D, Gabri E, Levi S, Albertini A. Immunochemical characterization of human liver and heart ferritins with monoclonal antibodies. Biochim Biophys Acta 1986; 872: 61-71.
    CrossrefPubMedSuche in Google Scholar
  • 54 Helmer-Citterich M, Ermanna R, Luzzago A, Tramontano A. Modelling Antibody-Antigen Interactions: Ferritin as a Case Study. Mol Immunol 1995; 32: 1001-10.
    CrossrefPubMedSuche in Google Scholar
  • 55 Samuel M, Samuel E, Villanueva GB. Histidine residues are essential for the surface binding and autoactivation of human coagulation Factor XII. Biochem. Biophys. Res. Commun 1993; 191: 110-17.
    PubMedSuche in Google Scholar
  • 56 Griep MA, Fujikawa K, Nelsestuen GL. Possible basis for the apparent surface selectivity of the contact activation of human blood coagulation Factor XII. Biochemistry 1986; 25: 6688-94.
    CrossrefPubMedSuche in Google Scholar