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Conformational Complexity of Complement Component C3

  • Conference paper
Current Topics in Complement

Part of the book series: Advances in Experimental Medicine and Biology ((volume 586))

7. Concluding Remarks

The structures of native C3 and its major fragment C3c have provided a wealth of structural insights into the central protein of the complement system. The proteolytic activation steps, generating the important fragments C3b and iC3b, are thought to induce significant conformational changes in the molecule, yielding protein molecules with distinct binding properties. The structures of C3 and C3c reveal the extent of conformational changes that may be expected. These structures together with the large amount of biochemical, mutagenesis, and binding data available on C3, its fragments, and the various interacting partners provide for the first time a detailed map of the various proposed binding sites. Still, many questions remain unanswered and additional structural data and sitedirected mutagenesis experiments, now made possible in a more rational way, are required to elucidate the complete complexity of the central component of the complement system.

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9. References

  1. M. J. Walport, Complement. First of two parts, N Engl J Med 344, 1058–1066 (2001).

    Article  PubMed  CAS  Google Scholar 

  2. M. C. Carroll, The complement system in regulation of adaptive immunity, Nat Immunol 5, 981–986 (2004).

    Article  PubMed  CAS  Google Scholar 

  3. A. Sahu and J. D. Lambris, Structure and biology of complement protein C3, a connecting link between innate and acquired immunity, Immunol Rev 180, 35–48 (2001).

    Article  PubMed  CAS  Google Scholar 

  4. Z. Fishelson, M. K. Pangburn and H. J. Muller-Eberhard, Characterization of the initial C3 convertase of the alternative pathway of human complement, J Immunol 132, 1430–1434 (1984).

    PubMed  CAS  Google Scholar 

  5. B. J. Janssen, E. G. Huizinga, H. C. Raaijmakers, A. Roos, M. R. Daha, K. Nilsson-Ekdahl, B. Nilsson and P. Gros, Structures of complement component C3 provide insights into the function and evolution of immunity, Nature 437, 505–511 (2005).

    Article  PubMed  CAS  Google Scholar 

  6. B. Bersch, J. F. Hernandez, D. Marion and G. J. Arlaud, Solution structure of the epidermal growth factor (EGF)-like module of human complement protease C1r, an atypical member of the EGF family, Biochemistry 37, 1204–1214 (1998).

    Article  PubMed  CAS  Google Scholar 

  7. M. Budayova-Spano, M. Lacroix, N. M. Thielens, G. J. Arlaud, J. C. Fontecilla-Camps and C. Gaboriaud, The crystal structure of the zymogen catalytic domain of complement protease C1r reveals that a disruptive mechanical stress is required to trigger activation of the C1 complex, Embo J 21, 231–239 (2002).

    Article  PubMed  CAS  Google Scholar 

  8. C. Gaboriaud, V. Rossi, I. Bally, G. J. Arlaud and J. C. Fontecilla-Camps, Crystal structure of the catalytic domain of human complement c1s: a serine protease with a handle, Embo J 19, 1755–1765 (2000).

    Article  PubMed  CAS  Google Scholar 

  9. L. A. Gregory, N. M. Thielens, G. J. Arlaud, J. C. Fontecilla-Camps and C. Gaboriaud, X-ray structure of the Ca2+-binding interaction domain of C1s: insights into the assembly of the C1 complex of complement, J Biol Chem 278, 32157–32164 (2003).

    Article  PubMed  CAS  Google Scholar 

  10. C. Gaboriaud, J. Juanhuix, A. Gruez, M. Lacroix, C. Darnault, D. Pignol, D. Verger, J. C. Fontecilla-Camps et al., The crystal structure of the globular head of complement protein C1q provides a basis for its versatile recognition properties, J Biol Chem 278, 46974–46982 (2003).

    Article  PubMed  CAS  Google Scholar 

  11. R. Huber, H. Scholze, E. P. Paques and J. Deisenhofer, Crystal structure analysis and molecular model of human C3a anaphylatoxin, Hoppe Seylers Z Physiol Chem 361, 1389–1399 (1980).

    PubMed  CAS  Google Scholar 

  12. B. Nagar, R. G. Jones, R. J. Diefenbach, D. E. Isenman and J. M. Rini, X-ray crystal structure of C3d: a C3 fragment and ligand for complement receptor 2, Science 280, 1277–1281 (1998).

    Article  PubMed  CAS  Google Scholar 

  13. J. M. van den Elsen, A. Martin, V. Wong, L. Clemenza, D. R. Rose and D. E. Isenman, X-ray crystal structure of the C4d fragment of human complement component C4, J Mol Biol 322, 1103–1115 (2002).

    Article  PubMed  CAS  Google Scholar 

  14. X. Zhang, W. Boyar, M. J. Toth, L. Wennogle and N. C. Gonnella, Structural definition of the C5a C terminus by two-dimensional nuclear magnetic resonance spectroscopy, Proteins 28, 261–267 (1997).

    Article  PubMed  CAS  Google Scholar 

  15. J. Bramham, C. T. Thai, D. C. Soares, D. Uhrin, R. T. Ogata and P. N. Barlow, Functional insights from the structure of the multifunctional C345C domain of C5 of complement, J Biol Chem 280, 10636–10645 (2005).

    Article  PubMed  CAS  Google Scholar 

  16. E. Ortlund, C. L. Parker, S. F. Schreck, S. Ginell, W. Minor, J. M. Sodetz and L. Lebioda, Crystal structure of human complement protein C8gamma at 1.2 Å resolution reveals a lipocalin fold and a distinct ligand binding site, Biochemistry 41, 7030–7037 (2002).

    Article  PubMed  CAS  Google Scholar 

  17. H. Jing, Y. Xu, M. Carson, D. Moore, K. J. Macon, J. E. Volanakis and S. V. Narayana, New structural motifs on the chymotrypsin fold and their potential roles in complement factor B, Embo J 19, 164–173 (2000).

    Article  PubMed  CAS  Google Scholar 

  18. A. A. Bhattacharya, M. L. Lupher, Jr., D. E. Staunton and R. C. Liddington, Crystal structure of the A domain from complement factor B reveals an integrin-like open conformation, Structure (Camb) 12, 371–378 (2004).

    Article  CAS  Google Scholar 

  19. K. Ponnuraj, Y. Xu, K. Macon, D. Moore, J. E. Volanakis and S. V. Narayana, Structural analysis of engineered Bb fragment of complement factor B: insights into the activation mechanism of the alternative pathway C3-convertase, Mol Cell 14, 17–28 (2004).

    Article  PubMed  CAS  Google Scholar 

  20. H. Jing, Y. S. Babu, D. Moore, J. M. Kilpatrick, X. Y. Liu, J. E. Volanakis and S. V. Narayana, Structures of native and complexed complement factor D: implications of the atypical His57 conformation and self-inhibitory loop in the regulation of specific serine protease activity, J Mol Biol 282, 1061–1081 (1998).

    Article  PubMed  CAS  Google Scholar 

  21. H. Feinberg, J. C. Uitdehaag, J. M. Davies, R. Wallis, K. Drickamer and W. I. Weis, Crystal structure of the CUB1-EGF-CUB2 region of mannose-binding protein associated serine protease-2, Embo J 22, 2348–2359 (2003).

    Article  PubMed  CAS  Google Scholar 

  22. V. Harmat, P. Gal, J. Kardos, K. Szilagyi, G. Ambrus, B. Vegh, G. Naray-Szabo and P. Zavodszky, The structure of MBL-associated serine protease-2 reveals that identical substrate specificities of C1s and MASP-2 are realized through different sets of enzyme-substrate interactions, J Mol Biol 342, 1533–1546 (2004).

    Article  PubMed  CAS  Google Scholar 

  23. L. A. Gregory, N. M. Thielens, M. Matsushita, R. Sorensen, G. J. Arlaud, J. C. Fontecilla-Camps and C. Gaboriaud, The X-ray structure of human mannanbinding lectin-associated protein 19 (MAp19) and its interaction site with mannanbinding lectin and L-ficolin, J Biol Chem 279, 29391–29397 (2004).

    Article  PubMed  CAS  Google Scholar 

  24. D. G. Norman, P. N. Barlow, M. Baron, A. J. Day, R. B. Sim and I. D. Campbell, Three-dimensional structure of a complement control protein module in solution, J Mol Biol 219, 717–725 (1991).

    Article  PubMed  CAS  Google Scholar 

  25. P. N. Barlow, D. G. Norman, A. Steinkasserer, T. J. Horne, J. Pearce, P. C. Driscoll, R. B. Sim and I. D. Campbell, Solution structure of the fifth repeat of factor H: a second example of the complement control protein module, Biochemistry 31, 3626–3634 (1992).

    Article  PubMed  CAS  Google Scholar 

  26. P. N. Barlow, A. Steinkasserer, D. G. Norman, B. Kieffer, A. P. Wiles, R. B. Sim and I. D. Campbell, Solution structure of a pair of complement modules by nuclear magnetic resonance, J Mol Biol 232, 268–284 (1993).

    Article  PubMed  CAS  Google Scholar 

  27. P. Williams, Y. Chaudhry, I. G. Goodfellow, J. Billington, R. Powell, O. B. Spiller, D. J. Evans and S. Lea, Mapping CD55 function. The structure of two pathogenbinding domains at 1.7 Å, J Biol Chem 278, 10691–10696 (2003).

    Article  PubMed  CAS  Google Scholar 

  28. S. Uhrinova, F. Lin, G. Ball, K. Bromek, D. Uhrin, M. E. Medof and P. N. Barlow, Solution structure of a functionally active fragment of decay-accelerating factor, Proc Natl Acad Sci USA 100, 4718–4723 (2003).

    Article  PubMed  CAS  Google Scholar 

  29. P. Lukacik, P. Roversi, J. White, D. Esser, G. P. Smith, J. Billington, P. A. Williams, P. M. Rudd et al., Complement regulation at the molecular level: the structure of decay-accelerating factor, Proc Natl Acad Sci USA 101, 1279–1284 (2004).

    Article  PubMed  CAS  Google Scholar 

  30. J. M. Casasnovas, M. Larvie and T. Stehle, Crystal structure of two CD46 domains reveals an extended measles virus-binding surface, Embo J 18, 2911–2922 (1999).

    Article  PubMed  CAS  Google Scholar 

  31. B. O. Smith, R. L. Mallin, M. Krych-Goldberg, X. Wang, R. E. Hauhart, K. Bromek, D. Uhrin, J. P. Atkinson et al., Structure of the C3b binding site of CR1 (CD35), the immune adherence receptor, Cell 108, 769–780 (2002).

    Article  PubMed  CAS  Google Scholar 

  32. A. E. Prota, D. R. Sage, T. Stehle and J. D. Fingeroth, The crystal structure of human CD21: Implications for Epstein-Barr virus and C3d binding, Proc Natl Acad Sci USA 99, 10641–10646 (2002).

    Article  PubMed  CAS  Google Scholar 

  33. J. O. Lee, P. Rieu, M. A. Arnaout and R. Liddington, Crystal structure of the A domain from the alpha subunit of integrin CR3 (CD11b/CD18), Cell 80, 631–638 (1995).

    Article  PubMed  CAS  Google Scholar 

  34. T. Vorup-Jensen, C. Ostermeier, M. Shimaoka, U. Hommel and T. A. Springer, Structure and allosteric regulation of the alpha X beta 2 integrin I domain, Proc Natl Acad Sci USA 100, 1873–1878 (2003).

    Article  PubMed  CAS  Google Scholar 

  35. C. M. Fletcher, R. A. Harrison, P. J. Lachmann and D. Neuhaus, Structure of a soluble, glycosylated form of the human complement regulatory protein CD59, Structure 2, 185–199 (1994).

    Article  PubMed  CAS  Google Scholar 

  36. G. Szakonyi, J. M. Guthridge, D. Li, K. Young, V. M. Holers and X. S. Chen, Structure of complement receptor 2 in complex with its C3d ligand, Science 292, 1725–1728 (2001).

    Article  PubMed  CAS  Google Scholar 

  37. A. P. Wiles, G. Shaw, J. Bright, A. Perczel, I. D. Campbell and P. N. Barlow, NMR studies of a viral protein that mimics the regulators of complement activation, J Mol Biol 272, 253–265 (1997).

    Article  PubMed  CAS  Google Scholar 

  38. K. H. Murthy, S. A. Smith, V. K. Ganesh, K. W. Judge, N. Mullin, P. N. Barlow, C. M. Ogata and G. J. Kotwal, Crystal structure of a complement control protein that regulates both pathways of complement activation and binds heparan sulfate proteoglycans, Cell 104, 301–311 (2001).

    Article  PubMed  CAS  Google Scholar 

  39. C. E. Henderson, K. Bromek, N. P. Mullin, B. O. Smith, D. Uhrin and P. N. Barlow, Solution structure and dynamics of the central CCP module pair of a poxvirus complement control protein, J Mol Biol 307, 323–339 (2001).

    Article  PubMed  CAS  Google Scholar 

  40. F. S. Cordes, P. Roversi, P. Kraiczy, M. M. Simon, V. Brade, O. Jahraus, R. Wallis, C. Skerka et al., A novel fold for the factor H-binding protein BbCRASP-1 of Borrelia burgdorferi, Nat Struct Mol Biol 12, 276–277 (2005).

    Article  PubMed  CAS  Google Scholar 

  41. P. J. Haas, C. J. de Haas, M. J. Poppelier, K. P. van Kessel, J. A. van Strijp, K. Dijkstra, R. M. Scheek, H. Fan et al., The Structure of the C5a Receptor-blocking Domain of Chemotaxis Inhibitory Protein of Staphylococcus aureus is Related to a Group of Immune Evasive Molecules, J Mol Biol (2005).

    Google Scholar 

  42. S. Hase, N. Kikuchi, T. Ikenaka and K. Inoue, Structures of sugar chains of the third component of human complement, J Biochem (Tokyo) 98, 863–874 (1985).

    CAS  Google Scholar 

  43. S. Hirani, J. D. Lambris and H. J. Muller-Eberhard, Structural analysis of the asparagine-linked oligosaccharides of human complement component C3, Biochem J 233, 613–616 (1986).

    PubMed  CAS  Google Scholar 

  44. B. F. Tack, R. A. Harrison, J. Janatova, M. L. Thomas and J. W. Prahl, Evidence for presence of an internal thiolester bond in third component of human complement, Proc Natl Acad Sci USA 77, 5764–5768 (1980).

    Article  PubMed  CAS  Google Scholar 

  45. K. Dolmer and L. Sottrup-Jensen, Disulfide bridges in human complement component C3b, FEBS Lett 315, 85–90 (1993).

    Article  PubMed  CAS  Google Scholar 

  46. J. Andersson, K. N. Ekdahl, R. Larsson, U. R. Nilsson and B. Nilsson, C3 adsorbed to a polymer surface can form an initiating alternative pathway convertase, J Immunol 168, 5786–5791 (2002).

    PubMed  CAS  Google Scholar 

  47. M. D. Crispin, G. E. Ritchie, A. J. Critchley, B. P. Morgan, I. A. Wilson, R. A. Dwek, R. B. Sim and P. M. Rudd, Monoglucosylated glycans in the secreted human complement component C3: implications for protein biosynthesis and structure, FEBS Lett 566, 270–274 (2004).

    Article  PubMed  CAS  Google Scholar 

  48. T. Mizuochi, R. W. Loveless, A. M. Lawson, W. Chai, P. J. Lachmann, R. A. Childs, S. Thiel and T. Feizi, A library of oligosaccharide probes (neoglycolipids) from N-glycosylated proteins reveals that conglutinin binds to certain complex-type as well as high mannose-type oligosaccharide chains, J Biol Chem 264, 13834–13839 (1989).

    PubMed  CAS  Google Scholar 

  49. A. W. Dodds, X. D. Ren, A. C. Willis and S. K. Law, The reaction mechanism of the internal thioester in the human complement component C4, Nature 379, 177–179 (1996).

    Article  PubMed  CAS  Google Scholar 

  50. S. K. Law and A. W. Dodds, The internal thioester and the covalent binding properties of the complement proteins C3 and C4, Protein Sci 6, 263–274 (1997).

    Article  PubMed  CAS  Google Scholar 

  51. M. Gadjeva, A. W. Dodds, A. Taniguchi-Sidle, A. C. Willis, D. E. Isenman and S. K. Law, The covalent binding reaction of complement component C3, J Immunol 161, 985–990 (1998).

    PubMed  CAS  Google Scholar 

  52. G. Zanotti, A. Bassetto, R. Battistutta, C. Folli, P. Arcidiaco, M. Stoppini and R. Berni, Structure at 1.44 A resolution of an N-terminally truncated form of the rat serum complement C3d fragment, Biochim Biophys Acta 1478, 232–238 (2000).

    PubMed  CAS  Google Scholar 

  53. D. E. Isenman, D. I. Kells, N. R. Cooper, H. J. Muller-Eberhard and M. K. Pangburn, Nucleophilic modification of human complement protein C3: correlation of conformational changes with acquisition of C3b-like functional properties, Biochemistry 20, 4458–4467 (1981).

    Article  PubMed  CAS  Google Scholar 

  54. J. D. Lambris, The multifunctional role of C3, the third component of complement, Immunol Today 9, 387–393 (1988).

    Article  PubMed  CAS  Google Scholar 

  55. Y. Xu, S. V. Narayana and J. E. Volanakis, Structural biology of the alternative pathway convertase, Immunol Rev 180, 123–135 (2001).

    Article  PubMed  CAS  Google Scholar 

  56. D. E. Hourcade, L. M. Wagner and T. J. Oglesby, Analysis of the short consensus repeats of human complement factor B by site-directed mutagenesis, J Biol Chem 270, 19716–19722 (1995).

    Article  PubMed  CAS  Google Scholar 

  57. P. Sanchez-Corral, L. C. Anton, J. M. Alcolea, G. Marques, A. Sanchez and F. Vivanco, Proteolytic activity of the different fragments of factor B on the third component of complement (C3). Involvement of the N-terminal domain of Bb in magnesium binding, Mol Immunol 27, 891–900 (1990).

    Article  PubMed  CAS  Google Scholar 

  58. D. E. Hourcade, L. M. Mitchell and T. J. Oglesby, Mutations of the type A domain of complement factor B that promote high-affinity C3b-binding, J Immunol 162, 2906–2911 (1999).

    PubMed  CAS  Google Scholar 

  59. J. Hinshelwood, D. I. Spencer, Y. J. Edwards and S. J. Perkins, Identification of the C3b binding site in a recombinant vWF-A domain of complement factor B by surface-enhanced laser desorption-ionisation affinity mass spectrometry and homology modelling: implications for the activity of factor B, J Mol Biol 294, 587–599 (1999).

    Article  PubMed  CAS  Google Scholar 

  60. D. E. Hourcade, L. Mitchell, L. A. Kuttner-Kondo, J. P. Atkinson and M. E. Medof, Decay-accelerating factor (DAF), complement receptor 1 (CR1), and factor H dissociate the complement AP C3 convertase (C3bBb) via sites on the type A domain of Bb, J Biol Chem 277, 1107–1112 (2002).

    Article  PubMed  CAS  Google Scholar 

  61. Z. Fishelson and H. J. Muller-Eberhard, C3 convertase of human complement: enhanced formation and stability of the enzyme generated with nickel instead of magnesium, J Immunol 129, 2603–2607 (1982).

    PubMed  CAS  Google Scholar 

  62. J. D. Lambris and H. J. Muller-Eberhard, Isolation and characterization of a 33,000-dalton fragment of complement Factor B with catalytic and C3b binding activity, J Biol Chem 259, 12685–12690 (1984).

    PubMed  CAS  Google Scholar 

  63. Z. Fishelson, Complement C3: a molecular mosaic of binding sites, Mol Immunol 28, 545–552 (1991).

    Article  PubMed  CAS  Google Scholar 

  64. A. Taniguchi-Sidle and D. E. Isenman, Interactions of human complement component C3 with factor B and with complement receptors type 1 (CR1, CD35) and type 3 (CR3, CD11b/CD18) involve an acidic sequence at the N-terminus of C3 alpha’-chain, J Immunol 153, 5285–5302 (1994).

    PubMed  CAS  Google Scholar 

  65. M. C. O’Keefe, L. H. Caporale and C. W. Vogel, A novel cleavage product of human complement component C3 with structural and functional properties of cobra venom factor, J Biol Chem 263, 12690–12697 (1988).

    PubMed  CAS  Google Scholar 

  66. J. M. Inal and J. A. Schifferli, Complement C2 receptor inhibitor trispanning and the beta-chain of C4 share a binding site for complement C2, J Immunol 168, 5213–5221 (2002).

    PubMed  CAS  Google Scholar 

  67. K. S. Oh, M. H. Kweon, K. H. Rhee, K. Ho Lee and H. C. Sung, Inhibition of complement activation by recombinant Sh-CRIT-ed1 analogues, Immunology 110, 73–79 (2003).

    Article  PubMed  CAS  Google Scholar 

  68. J. Kolln, E. Spillner, J. Andra, K. Klensang and R. Bredehorst, Complement inactivation by recombinant human C3 derivatives, J Immunol 173, 5540–5545 (2004).

    PubMed  Google Scholar 

  69. J. Kolln, R. Bredehorst and E. Spillner, Engineering of human complement component C3 for catalytic inhibition of complement, Immunol Lett 98, 49–56 (2005).

    Article  PubMed  CAS  Google Scholar 

  70. J. D. Becherer, J. Alsenz, I. Esparza, C. E. Hack and J. D. Lambris, Segment spanning residues 727–768 of the complement C3 sequence contains a neoantigenic site and accommodates the binding of CR1, factor H, and factor B, Biochemistry 31, 1787–1794 (1992).

    Article  PubMed  CAS  Google Scholar 

  71. R. T. Ogata, R. Ai and P. J. Low, Active sites in complement component C3 mapped by mutations at indels, J Immunol 161, 4785–4794 (1998).

    PubMed  CAS  Google Scholar 

  72. Z. Sun, K. B. Reid and S. J. Perkins, The dimeric and trimeric solution structures of the multidomain complement protein properdin by X-ray scattering, analytical ultracentrifugation and constrained modelling, J Mol Biol 343, 1327–1343 (2004).

    Article  PubMed  CAS  Google Scholar 

  73. M. K. Pangburn, Analysis of the natural polymeric forms of human properdin and their functions in complement activation, J Immunol 142, 202–207 (1989).

    PubMed  CAS  Google Scholar 

  74. D. T. Fearon and K. F. Austen, Properdin: binding to C3b and stabilization of the C3b-dependent C3 convertase, J Exp Med 142, 856–863 (1975).

    Article  PubMed  CAS  Google Scholar 

  75. M. E. Daoudaki, J. D. Becherer and J. D. Lambris, A 34-amino acid peptide of the third component of complement mediates properdin binding, J Immunol 140, 1577–1580 (1988).

    PubMed  CAS  Google Scholar 

  76. R. G. DiScipio, The binding of human complement proteins C5, factor B, beta 1H and properdin to complement fragment C3b on zymosan, Biochem J 199, 485–496 (1981).

    PubMed  CAS  Google Scholar 

  77. J. M. Higgins, H. Wiedemann, R. Timpl and K. B. Reid, Characterization of mutant forms of recombinant human properdin lacking single thrombospondin type I repeats. Identification of modules important for function, J Immunol 155, 5777–5785 (1995).

    PubMed  CAS  Google Scholar 

  78. S. H. Rooijakkers, M. Ruyken, A. Roos, M. R. Daha, J. S. Presanis, R. B. Sim, W. J. van Wamel, K. P. van Kessel et al., Immune evasion by a staphylococcal complement inhibitor that acts on C3 convertases, Nat Immunol 6, 920–927 (2005).

    Article  PubMed  CAS  Google Scholar 

  79. M. D. Kirkitadze and P. N. Barlow, Structure and flexibility of the multiple domain proteins that regulate complement activation, Immunol Rev 180, 146–161 (2001).

    Article  PubMed  CAS  Google Scholar 

  80. P. Kraiczy, C. Skerka, M. Kirschfink, P. F. Zipfel and V. Brade, Mechanism of complement resistance of pathogenic Borrelia burgdorferi isolates, Int Immunopharmacol 1, 393–401 (2001).

    Article  PubMed  CAS  Google Scholar 

  81. P. Jha and G. J. Kotwal, Vaccinia complement control protein: multi-functional protein and a potential wonder drug, J Biosci 28, 265–271 (2003).

    Article  PubMed  CAS  Google Scholar 

  82. W. G. Brodbeck, D. Liu, J. Sperry, C. Mold and M. E. Medof, Localization of classical and alternative pathway regulatory activity within the decay-accelerating factor, J Immunol 156, 2528–2533 (1996).

    PubMed  CAS  Google Scholar 

  83. M. Krych, R. Hauhart and J. P. Atkinson, Structure-function analysis of the active sites of complement receptor type 1, J Biol Chem 273, 8623–8629 (1998).

    Article  PubMed  CAS  Google Scholar 

  84. S. Kuhn and P. F. Zipfel, Mapping of the domains required for decay acceleration activity of the human factor H-like protein 1 and factor H, Eur J Immunol 26, 2383–2387 (1996).

    PubMed  CAS  Google Scholar 

  85. K. Yazdanbakhsh and A. Scaradavou, CR1-based inhibitors for prevention of complement-mediated immune hemolysis, Drug News Perspect 17, 314–320 (2004).

    Article  PubMed  CAS  Google Scholar 

  86. J. D. Lambris, Z. Lao, T. J. Oglesby, J. P. Atkinson, C. E. Hack and J. D. Becherer, Dissection of CR1, factor H, membrane cofactor protein, and factor B binding and functional sites in the third complement component, J Immunol 156, 4821–4832 (1996).

    PubMed  CAS  Google Scholar 

  87. A. E. Oran and D. E. Isenman, Identification of residues within the 727–767 segment of human complement component C3 important for its interaction with factor H and with complement receptor 1 (CR1, CD35), J Biol Chem 274, 5120–5130 (1999).

    Article  PubMed  CAS  Google Scholar 

  88. J. M. Weiler, M. R. Daha, K. F. Austen and D. T. Fearon, Control of the amplification convertase of complement by the plasma protein beta1H, Proc Natl Acad Sci USA 73, 3268–3272 (1976).

    Article  PubMed  CAS  Google Scholar 

  89. J. D. Lambris, D. Avila, J. D. Becherer and H. J. Muller-Eberhard, A discontinuous factor H binding site in the third component of complement as delineated by synthetic peptides, J Biol Chem 263, 12147–12150 (1988).

    PubMed  CAS  Google Scholar 

  90. T. S. Jokiranta, J. Hellwage, V. Koistinen, P. F. Zipfel and S. Meri, Each of the three binding sites on complement factor H interacts with a distinct site on C3b, J Biol Chem 275, 27657–27662 (2000).

    PubMed  CAS  Google Scholar 

  91. C. L. Harris, R. J. Abbott, R. A. Smith, B. P. Morgan and S. M. Lea, Molecular dissection of interactions between components of the alternative pathway of complement and decay accelerating factor (CD55), J Biol Chem 280, 2569–2578 (2005).

    Article  PubMed  CAS  Google Scholar 

  92. M. Krych, L. Clemenza, D. Howdeshell, R. Hauhart, D. Hourcade and J. P. Atkinson, Analysis of the functional domains of complement receptor type 1 (C3b/C4b receptor; CD35) by substitution mutagenesis, J Biol Chem 269, 13273–13278 (1994).

    PubMed  CAS  Google Scholar 

  93. M. Krych-Goldberg, R. E. Hauhart, V. B. Subramanian, B. M. Yurcisin 2nd, D. L. Crimmins, D. E. Hourcade and J. P. Atkinson, Decay accelerating activity of complement receptor type 1 (CD35). Two active sites are required for dissociating C5 convertases, J Biol Chem 274, 31160–31168 (1999).

    Article  PubMed  CAS  Google Scholar 

  94. A. M. Blom, A. F. Zadura, B. O. Villoutreix and B. Dahlback, Positively charged amino acids at the interface between alpha-chain CCP1 and CCP2 of C4BP are required for regulation of the classical C3-convertase, Mol Immunol 37, 445–453 (2000).

    Article  PubMed  CAS  Google Scholar 

  95. L. A. Kuttner-Kondo, L. Mitchell, D. E. Hourcade and M. E. Medof, Characterization of the active sites in decay-accelerating factor, J Immunol 167, 2164–2171 (2001).

    PubMed  CAS  Google Scholar 

  96. M. K. Pangburn, R. D. Schreiber and H. J. Muller-Eberhard, Human complement C3b inactivator: isolation, characterization, and demonstration of an absolute requirement for the serum protein beta1H for cleavage of C3b and C4b in solution, J Exp Med 146, 257–270 (1977).

    Article  PubMed  CAS  Google Scholar 

  97. G. D. Ross, J. D. Lambris, J. A. Cain and S. L. Newman, Generation of three different fragments of bound C3 with purified factor I or serum. I. Requirements for factor H vs CR1 cofactor activity, J Immunol 129, 2051–2060 (1982).

    PubMed  CAS  Google Scholar 

  98. T. Seya, J. R. Turner and J. P. Atkinson, Purification and characterization of a membrane protein (gp45-70) that is a cofactor for cleavage of C3b and C4b, J Exp Med 163, 837–855 (1986).

    Article  PubMed  CAS  Google Scholar 

  99. R. G. Medicus, J. Melamed and M. A. Arnaout, Role of human factor I and C3b receptor in the cleavage of surface-bound C3bi molecules, Eur J Immunol 13, 465–470 (1983).

    PubMed  CAS  Google Scholar 

  100. M. K. Liszewski, T. W. Post and J. P. Atkinson, Membrane cofactor protein (MCP or CD46): newest member of the regulators of complement activation gene cluster, Annu Rev Immunol 9, 431–455 (1991).

    Article  PubMed  CAS  Google Scholar 

  101. E. M. Adams, M. C. Brown, M. Nunge, M. Krych and J. P. Atkinson, Contribution of the repeating domains of membrane cofactor protein (CD46) of the complement system to ligand binding and cofactor activity, J Immunol 147, 3005–3011 (1991).

    PubMed  CAS  Google Scholar 

  102. R. A. Harrison and P. J. Lachmann, Novel cleavage products of the third component of human complement, Mol Immunol 17, 219–228 (1980).

    Article  PubMed  CAS  Google Scholar 

  103. P. J. Lachmann, M. K. Pangburn and R. G. Oldroyd, Breakdown of C3 after complement activation. Identification of a new fragment C3g, using monoclonal antibodies, J Exp Med 156, 205–216 (1982).

    Article  PubMed  CAS  Google Scholar 

  104. D. E. Isenman, Conformational changes accompanying proteolytic cleavage of human complement protein C3b by the regulatory enzyme factor I and its cofactor H. Spectroscopic and enzymological studies, J Biol Chem 258, 4238–4244 (1983).

    PubMed  CAS  Google Scholar 

  105. T. Ueda, P. Rieu, J. Brayer and M. A. Arnaout, Identification of the complement iC3b binding site in the beta 2 integrin CR3 (CD11b/CD18), Proc Natl Acad Sci USA 91, 10680–10684 (1994).

    Article  PubMed  CAS  Google Scholar 

  106. T. Kamata, R. Wright and Y. Takada, Critical threonine and aspartic acid residues within the I domains of beta 2 integrins for interactions with intercellular adhesion molecule 1 (ICAM-1) and C3bi, J Biol Chem 270, 12531–12535 (1995).

    Article  PubMed  CAS  Google Scholar 

  107. S. L. McGuire and M. L. Bajt, Distinct ligand binding sites in the I domain of integrin alpha M beta 2 that differentially affect a divalent cation-dependent conformation, J Biol Chem 270, 25866–25871 (1995).

    Article  PubMed  CAS  Google Scholar 

  108. V. A. Ustinov and E. F. Plow, Identity of the amino acid residues involved in C3bi binding to the I-domain supports a mosaic model to explain the broad ligand repertoire of integrin alpha M beta 2, Biochemistry 44, 4357–4364 (2005).

    Article  PubMed  CAS  Google Scholar 

  109. J. Emsley, C. G. Knight, R. W. Farndale, M. J. Barnes and R. C. Liddington, Structural basis of collagen recognition by integrin alpha2beta1, Cell 101, 47–56 (2000).

    Article  PubMed  CAS  Google Scholar 

  110. M. Shimaoka, T. Xiao, J. H. Liu, Y. Yang, Y. Dong, C. D. Jun, A. McCormack, R. Zhang et al., Structures of the alpha L I domain and its complex with ICAM-1 reveal a shape-shifting pathway for integrin regulation, Cell 112, 99–111 (2003).

    Article  PubMed  CAS  Google Scholar 

  111. J. Emsley, S. L. King, J. M. Bergelson and R. C. Liddington, Crystal structure of the I domain from integrin alpha2beta1, J Biol Chem 272, 28512–28517 (1997).

    Article  PubMed  CAS  Google Scholar 

  112. Z. Fishelson, M. K. Pangburn and H. J. Muller-Eberhard, C3 convertase of the alternative complement pathway. Demonstration of an active, stable C3b, Bb (Ni) complex, J Biol Chem 258, 7411–7415 (1983).

    PubMed  CAS  Google Scholar 

  113. J. Hinshelwood and S. J. Perkins, Metal-dependent conformational changes in a recombinant vWF-A domain from human factor B: a solution study by circular dichroism, fourier transform infrared and (1)H NMR spectroscopy, J Mol Biol 298, 135–147 (2000).

    Article  PubMed  CAS  Google Scholar 

  114. Y. M. Xiong and L. Zhang, Structure-function of the putative I-domain within the integrin beta 2 subunit, J Biol Chem 276, 19340–19349 (2001).

    Article  PubMed  CAS  Google Scholar 

  115. Y. Li and L. Zhang, The fourth blade within the beta-propeller is involved specifically in C3bi recognition by integrin alpha M beta 2, J Biol Chem 278, 34395–34402 (2003).

    Article  PubMed  CAS  Google Scholar 

  116. C. A. Lowell, L. B. Klickstein, R. H. Carter, J. A. Mitchell, D. T. Fearon and J. M. Ahearn, Mapping of the Epstein-Barr virus and C3dg binding sites to a common domain on complement receptor type 2, J Exp Med 170, 1931–1946 (1989).

    Article  PubMed  CAS  Google Scholar 

  117. L. Clemenza and D. E. Isenman, Structure-guided identification of C3d residues essential for its binding to complement receptor 2 (CD21), J Immunol 165, 3839–3848 (2000).

    PubMed  CAS  Google Scholar 

  118. H. Molina, S. J. Perkins, J. Guthridge, J. Gorka, T. Kinoshita and V. M. Holers, Characterization of a complement receptor 2 (CR2, CD21) ligand binding site for C3. An initial model of ligand interaction with two linked short consensus repeat modules, J Immunol 154, 5426–5435 (1995).

    PubMed  CAS  Google Scholar 

  119. J. D. Lambris, V. S. Ganu, S. Hirani and H. J. Muller-Eberhard, Mapping of the C3d receptor (CR2)-binding site and a neoantigenic site in the C3d domain of the third component of complement, Proc Natl Acad Sci USA 82, 4235–4239 (1985).

    Article  PubMed  CAS  Google Scholar 

  120. I. Esparza, J. D. Becherer, J. Alsenz, A. De la Hera, Z. Lao, C. D. Tsoukas and J. D. Lambris, Evidence for multiple sites of interaction in C3 for complement receptor type 2 (C3d/EBV receptor, CD21), Eur J Immunol 21, 2829–2838 (1991).

    PubMed  CAS  Google Scholar 

  121. R. J. Diefenbach and D. E. Isenman, Mutation of residues in the C3dg region of human complement component C3 corresponding to a proposed binding site for complement receptor type 2 (CR2, CD21) does not abolish binding of iC3b or C3dg to CR2, J Immunol 154, 2303–2320 (1995).

    PubMed  CAS  Google Scholar 

  122. K. R. Kalli, J. M. Ahearn and D. T. Fearon, Interaction of iC3b with recombinant isotypic and chimeric forms of CR2, J Immunol 147, 590–594 (1991).

    PubMed  CAS  Google Scholar 

  123. M. R. Sarrias, S. Franchini, G. Canziani, E. Argyropoulos, W. T. Moore, A. Sahu and J. D. Lambris, Kinetic analysis of the interactions of complement receptor 2 (CR2, CD21) with its ligands C3d, iC3b, and the EBV glycoprotein gp350/220, J Immunol 167, 1490–1499 (2001).

    PubMed  CAS  Google Scholar 

  124. D. Morikis and J. D. Lambris, The electrostatic nature of C3d-complement receptor 2 association, J Immunol 172, 7537–7547 (2004).

    PubMed  CAS  Google Scholar 

  125. J. P. Hannan, K. A. Young, J. M. Guthridge, R. Asokan, G. Szakonyi, X. S. Chen and V. M. Holers, Mutational analysis of the complement receptor type 2 (CR2/CD21)-C3d interaction reveals a putative charged SCR1 binding site for C3d, J Mol Biol 346, 845–858 (2005).

    Article  PubMed  CAS  Google Scholar 

  126. H. E. Gilbert, J. T. Eaton, J. P. Hannan, V. M. Holers and S. J. Perkins, Solution structure of the complex between CR2 SCR 1-2 and C3d of human complement: an X-ray scattering and sedimentation modelling study, J Mol Biol 346, 859–873 (2005).

    Article  PubMed  CAS  Google Scholar 

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  1. Crystal and Structural Chemistry, Bijvoet Center for Biomolecular Research, Dept. of Chemistry, Faculty of Science, Utrecht University, Padualaan 8, 3584 CH, Utrecht, The Netherlands

    Bert J. C. Janssen & Piet Gros

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  1. Bert J. C. Janssen
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  2. Piet Gros
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  1. University of Pennsylvania, Philadelphia, PA, 19107

    John D. Lambris Ph.D. (Professor of Pathology & Laboratory Medicine) (Professor of Pathology & Laboratory Medicine)

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Janssen, B.J.C., Gros, P. (2006). Conformational Complexity of Complement Component C3. In: Lambris, J.D. (eds) Current Topics in Complement. Advances in Experimental Medicine and Biology, vol 586. Springer, Boston, MA. https://doi.org/10.1007/0-387-34134-X_20

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