Monospecific inhibitors show that both mannan-binding lectin-associated serine protease-1 (MASP-1) and -2 are essential for lectin pathway activation and reveal structural plasticity of MASP-2

Journal of Biological Chemistry

Volumn 287, Issue 24, 2012, Pages 20290-20300

  Héja, Dávid ^a   Harmats, Veronika ^a   Fodor, Krisztián ^b   Wilmanns, Matthias ^b   Dobó, József ^c   Kékesi, Katalin A ^a   Závodszky, Péter ^c   Gál, Péter ^c   Pál, Gábor ^a  

^a EÖTVÖS LORÁND UNIVERSITY   (Hungary)

^b EUROPEAN MOLECULAR BIOLOGY LABORATORY   (Germany)

^c INSTITUTE OF EXPERIMENTAL MEDICINE   (Hungary)

Author keywords

[No Author keywords available]

Indexed keywords

COMPLEMENT SYSTEMS; COMPLEX STRUCTURE; CONFORMATIONAL SELECTION; HEART ATTACK; INDUCED FIT; ISCHEMIA-REPERFUSION INJURY; PATHWAY COMPONENTS; SERINE PROTEASE; SUBSTRATE-LIKE INHIBITORS; TARGET BINDING; TISSUE DAMAGE;

AMINO ACIDS; PATHOGENS; PATTERN RECOGNITION; PLASTICITY; TISSUE;

CHEMICAL ACTIVATION;

LECTIN; MANNAN BINDING LECTIN ASSOCIATED SERINE PROTEINASE; MANNAN BINDING LECTIN ASSOCIATED SERINE PROTEINASE 1; MANNAN BINDING LECTIN ASSOCIATED SERINE PROTEINASE 2; PROTEINASE INHIBITOR; SCHISTOCERCA GREGARIA PROTEINASE INHIBITOR 1; SCHISTOCERCA GREGARIA PROTEINASE INHIBITOR 2; UNCLASSIFIED DRUG;

ARTICLE; BINDING SITE; COMPLEMENT ACTIVATION; COMPLEMENT LECTIN PATHWAY; COMPLEX FORMATION; CONTROLLED STUDY; ENZYME ANALYSIS; ENZYME CONFORMATION; ENZYME SPECIFICITY; ENZYME STRUCTURE; ENZYME SUBSTRATE COMPLEX; NONHUMAN; PHAGE DISPLAY; PRIORITY JOURNAL; PROTEIN FUNCTION; PROTEINASE INHIBITION; SIGNAL TRANSDUCTION;

COMPLEMENT PATHWAY, MANNOSE-BINDING LECTIN; CRYSTALLOGRAPHY, X-RAY; HUMANS; MANNOSE-BINDING PROTEIN-ASSOCIATED SERINE PROTEASES; PROTEASE INHIBITORS; PROTEIN STRUCTURE, QUATERNARY; PROTEIN STRUCTURE, TERTIARY; STRUCTURE-ACTIVITY RELATIONSHIP;

EID: 84862023318     PISSN: 00219258     EISSN: 1083351X     Source Type: Journal    
DOI: 10.1074/jbc.M112.354332     Document Type: Article

References (65)

1. Ricklin, D., Hajishengallis, G., Yang, K., and Lambris, J. D. (2010) Complement. A key system for immune surveillance and homeostasis. Nat. Immunol. 11, 785-797
2. Thiel, S. (2007) Complement activating soluble pattern recognition molecules with collagen-like regions, mannan binding lectin, ficolins, and associated proteins. Mol. Immunol. 44, 3875-3888
3. Hansen, S., Selman, L., Palaniyar, N., Ziegler, K., Brandt, J., Kliem, A., Jonasson, M., Skjoedt, M. O., Nielsen, O., Hartshorn, K., Jørgensen, T. J., Skjødt, K., and Holmskov, U. (2010) Collectin 11 (CL-11, CL-K1) is a MASP-1/3-associated plasma collectin with microbial-binding activity. J. Immunol. 185, 6096-6104
4. Gál, P., Dobó, J., Závodszky, P., and Sim, R. B. (2009) Early complement proteases: C1r, C1s, and MASPs. A structural insight into activation and functions. Mol. Immunol. 46, 2745-2752
5. Degn, S. E., Hansen, A. G., Steffensen, R., Jacobsen, C., Jensenius, J. C., and Thiel, S. (2009) MAp44, a human protein associated with pattern recognition molecules of the complement system and regulating the lectin pathway of complement activation. J. Immunol. 183, 7371-7378
6. Skjoedt, M. O., Hummelshoj, T., Palarasah, Y., Honore, C., Koch, C., Skjodt, K., and Garred, P. (2010) A novel mannose-binding lectin/ficolin- associated protein is highly expressed in heart and skeletal muscle tissues and inhibits complement activation. J. Biol. Chem. 285, 8234-8243
7. Fujita, T. (2002) Evolution of the lectin-complement pathway and its role in innate immunity. Nat. Rev. Immunol. 2, 346-353
8. Kocsis, A., Kékesi, K. A., Szász, R., Végh, B. M., Balczer, J., Dobó, J., Závodszky, P., Gál, P., and Pál, G. (2010) Selective inhibition of the lectin pathway of complement with phage display-selected peptides against mannose-binding lectin-associated serine protease-1 (MASP-1) and -2. Significant contribution of MASP-1 to lectin pathway activation. J. Immunol. 185, 4169-4178
9. Szenthe, B., Patthy, A., Gáspári, Z., Kékesi, A. K., Gráf, L., and Pál, G. (2007) When the surface tells what lies beneath. Combinatorial phage-display mutagenesis reveals complex networks of surface-core interactions in the pacifastin protease inhibitor family. J. Mol. Biol. 370, 63-79 (Pubitemid 46817568)
10. Sidhu, S. S., Lowman, H. B., Cunningham, B. C., and Wells, J. A. (2000) Phage display for selection of novel binding peptides. Methods Enzymol. 328, 333-363
11. Dobó, J., Harmat, V., Beinrohr, L., Sebestyén, E., Závodszky, P., and Gál, P. (2009) MASP-1, a promiscuous complement protease. Structure of its catalytic region reveals the basis of its broad specificity. J. Immunol. 183, 1207-1214
12. Ambrus, G., Gál, P., Kojima, M., Szilágyi, K., Balczer, J., Antal, J., Gráf, L., Laich, A., Moffatt, B. E., Schwaeble, W., Sim, R. B., and Závodszky, P. (2003) Natural substrates and inhibitors of mannan-binding lectin-associated serine protease-1 and -2. A study on recombinant catalytic fragments. J. Immunol. 170, 1374-1382 (Pubitemid 36139504)
13. Crooks, G. E., Hon, G., Chandonia, J. M., and Brenner, S. E. (2004) WebLogo. A sequence logo generator. Genome Res. 14, 1188-1190
14. Szabó, A., Héja, D., Szakács, D., Zboray, K., Kékesi, K. A., Radisky, E. S., Sahin-Tóth, M., and Pál, G. (2011) High affinity small protein inhibitors of human chymotrypsin C (CTRC) selected by phage display reveal unusual preference for P4' acidic residues. J. Biol. Chem. 286, 22535-22545
15. Kabsch, W. (1993) Automatic processing of rotation diffraction data from crystals of initially unknown symmetry and cell constants. J. Appl. Crystallogr. 26, 795-800
16. Vagin, A., and Teplyakov, A. (1997) MOLREP: an Automated Program for Molecular Replacement. J. Appl. Crystallogr. 30, 1022-1025 (Pubitemid 127485985)
17. Dodson, E. J., Winn, M., and Ralph, A. (1997) Collaborative Computational Project, number 4. Providing programs for protein crystallography. Methods Enzymol. 277, 620-633 (Pubitemid 27390943)
18. Kabsch, W. (2010) XDS. Acta Crystallogr. D Biol. Crystallogr. 66, 125-132
19. Evans, P. R. (1997) Joint CCP4 and ESF-EAMBC Newsletter on Protein Crytallography 33, 22-24
20. Read, R. J. (2001) Pushing the boundaries of molecular replacement with maximum likelihood. Acta Crystallogr. D Biol. Crystallogr. 57, 1373-1382
21. Emsley, P., and Cowtan, K. (2004) Coot. Model-building tools for molecular graphics. Acta Crystallogr. D Biol. Crystallogr. 60, 2126-2132 (Pubitemid 41742764)
22. Murshudov, G. N., Vagin, A. A., and Dodson, E. J. (1997) Refinement of macromolecular structures by the maximum-likelihood method. Acta Crystallogr. D Biol. Crystallogr. 53, 240-255 (Pubitemid 27235885)
23. Winn, M. D., Isupov, M. N., and Murshudov, G. N. (2001) Use of TLS parameters to model anisotropic displacements in macromolecular refinement. Acta Crystallogr. D Biol. Crystallogr. 57, 122-133 (Pubitemid 32062682)
24. Laskowski, R. A., Macarthur, M. W., Moss, D. S., and Thornton, J. M. (1993) PROCHECK: a program to check the stereochemical quality of protein sructures. J. Appl. Crystallogr. 26, 283-291
25. Vaguine, A. A., Richelle, J., and Wodak, S. J. (1999) SFCHECK. A unified set of procedures for evaluating the quality of macromolecular structure-factor data and their agreement with the atomic model. Acta Crystallogr. D Biol. Crystallogr. 55, 191-205 (Pubitemid 29053816)
26. Chen, V. B., Arendall, W. B., 3rd, Headd, J. J., Keedy, D. A., Immormino, R. M., Kapral, G. J., Murray, L. W., Richardson, J. S., and Richardson, D. C. (2010) MolProbity. All-atom structure validation for macromolecular crystallography. Acta Crystallogr. D Biol. Crystallogr. 66, 12-21
27. Krissinel, E., and Henrick, K. (2007) Inference of macromolecular assemblies from crystalline state. J. Mol. Biol. 372, 774-797 (Pubitemid 47321791)
28. DeLano, W. L. (2002) The PyMOL Molecular Graphics System, DeLano Scientific LLC, San Carlos, CA
29. Breugelmans, B., Simonet, G., van Hoef, V., Van Soest, S., and Vanden Broeck, J. (2009) Pacifastin-related peptides. Structural and functional characteristics of a family of serine peptidase inhibitors. Peptides 30, 622-632
30. Malik, Z., Amir, S., Pál, G., Buzás, Z., Várallyay, E., Antal, J., Szilágyi, Z., Vékey, K., Asbóth, B., Patthy, A., and Gráf, L. (1999) Proteinase inhibitors from desert locust, Schistocerca gregaria. Engineering of both P(1) and P(1)' residues converts a potent chymotrypsin inhibitor to a potent trypsin inhibitor. Biochim. Biophys. Acta 1434, 143-150 (Pubitemid 29521341)
31. Wahlgren, W. Y., Pál, G., Kardos, J., Porrogi, P., Szenthe, B., Patthy, A., Gráf, L., and Katona, G. (2011) The catalytic aspartate is protonated in the Michaelis complex formed between trypsin and an in vitro evolved substrate-like inhibitor.Arefined mechanism of serine protease action. J. Biol. Chem. 286, 3587-3596
32. Schechter, I., and Berger, A. (1967) On the size of the active site in proteases. I. Papain. Biochem. Biophys. Res. Commun. 27, 157-162
33. Pál, G., Fong, S. Y., Kossiakoff, A. A., and Sidhu, S. S. (2005) Alternative views of functional protein binding epitopes obtained by combinatorial shotgun scanning mutagenesis. Protein Sci. 14, 2405-2413 (Pubitemid 41252808)
34. Pál, G., Kouadio, J. L., Artis, D. R., Kossiakoff, A. A., and Sidhu, S. S. (2006) Comprehensive and quantitative mapping of energy landscapes for protein- protein interactions by rapid combinatorial scanning. J. Biol. Chem. 281, 22378-22385 (Pubitemid 44181940)
35. Pal, G., Kossiakoff, A. A., and Sidhu, S. S. (2003) The functional binding epitope of a high affinity variant of human growth hormone mapped by shotgun alanine-scanning mutagenesis. Insights into the mechanisms responsible for improved affinity. J. Mol. Biol. 332, 195-204 (Pubitemid 36999741)
36. Pál, G., Ultsch, M. H., Clark, K. P., Currell, B., Kossiakoff, A. A., and Sidhu, S. S. (2005) Intramolecular cooperativity in a protein binding site assessed by combinatorial shotgun scanning mutagenesis. J. Mol. Biol. 347, 489-494 (Pubitemid 40332359)
37. Weiss, G. A., Watanabe, C. K., Zhong, A., Goddard, A., and Sidhu, S. S. (2000) Rapid mapping of protein functional epitopes by combinatorial alanine scanning. Proc. Natl. Acad. Sci. U.S.A. 97, 8950-8954 (Pubitemid 30626654)
38. Seelen, M. A., Roos, A., Wieslander, J., Mollnes, T. E., Sjöholm, A. G., Wurzner, R., Loos, M., Tedesco, F., Sim, R. B., Garred, P., Alexopoulos, E., Turner, M. W., and Daha, M. R. (2005) Functional analysis of the classical, alternative, and MBL pathways of the complement system. Standardization and validation of a simple ELISA. J. Immunol. Methods 296, 187-198 (Pubitemid 40174752)
39. Harmat, V., Gál, P., Kardos, J., Szilágyi, K., Ambrus, G., Végh, B., Náray- Szabó, G., and Závodszky, P. (2004) 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 (Pubitemid 39208676)
40. Koshland, D. E. (1958) Application of a theory of enzyme specificity to protein synthesis. Proc. Natl. Acad. Sci. U.S.A. 44, 98-104
41. Straub, F. B. (1964) Formation of the secondary and tertiary structure of enzymes. Adv. Enzymol. Relat. Areas Mol. Biol. 26, 89-114
42. Roussel, A., Mathieu, M., Dobbs, A., Luu, B., Cambillau, C., and Kellenberger, C. (2001) Complexation of two proteic insect inhibitors to the active site of chymotrypsin suggests decoupled roles for binding and selectivity. J. Biol. Chem. 276, 38893-38898
43. Leone, P., Roussel, A., and Kellenberger, C. (2008) Structure of Locusta migratoria protease inhibitor 3 (LMPI-3) in complex with Fusarium oxysporum trypsin. Acta Crystallogr. D Biol. Crystallogr. 64, 1165-1171
44. Fodor, K., Harmat, V., Hetényi, C., Kardos, J., Antal, J., Perczel, A., Patthy, A., Katona, G., and Gráf, L. (2005) Extended intermolecular interactions in a serine protease-canonical inhibitor complex account for strong and highly specific inhibition. J. Mol. Biol. 350, 156-169 (Pubitemid 40804739)
45. Perona, J. J., and Craik, C. S. (1997) Evolutionary divergence of substrate specificity within the chymotrypsin-like serine protease fold. J. Biol. Chem. 272, 29987-29990 (Pubitemid 27512189)
46. Gáspári, Z., Patthy, A., Gráf, L., and Perczel, A. (2002) Comparative structure analysis of proteinase inhibitors from the desert locust, Schistocerca gregaria. Eur. J. Biochem. 269, 527-537 (Pubitemid 34128010)
47. Szenthe, B., Gáspári, Z., Nagy, A., Perczel, A., and Gráf, L. (2004) Same fold with different mobility. Backbone dynamics of small protease inhibitors from the desert locust, Schistocerca gregaria. Biochemistry 43, 3376-3384 (Pubitemid 38391694)
48. Fodor, K., Harmat, V., Neutze, R., Szilágyi, L., Gráf, L., and Katona, G. (2006) Enzyme-substrate hydrogen bond shortening during the acylation phase of serine protease catalysis. Biochemistry 45, 2114-2121 (Pubitemid 43271311)
49. Hajela, K., Kojima, M., Ambrus, G., Wong, K. H., Moffatt, B. E., Ferluga, J., Hajela, S., Gál, P., and Sim, R. B. (2002) The biological functions of MBL-associated serine proteases (MASPs). Immunobiology 205, 467-475 (Pubitemid 35153962)
50. Megyeri, M., Makó, V., Beinrohr, L., Doleschall, Z., Prohászka, Z., Cervenak, L., Závodszky, P., and Gál, P. (2009) Complement protease MASP-1 activates human endothelial cells. PAR4 activation is a link between complement and endothelial function. J. Immunol. 183, 3409-3416
51. Thiel, S., Vorup-Jensen, T., Stover, C. M., Schwaeble, W., Laursen, S. B., Poulsen, K., Willis, A. C., Eggleton, P., Hansen, S., Holmskov, U., Reid, K. B., and Jensenius, J. C. (1997) A second serine protease associated with mannan-binding lectin that activates complement. Nature 386, 506-510 (Pubitemid 27164078)
52. Davis, A. E., 3rd, Lu, F., and Mejia, P. (2010) C1 inhibitor, a multi-functional serine protease inhibitor. Thromb. Haemost. 104, 886-893
53. Vorup-Jensen, T., Petersen, S. V., Hansen, A. G., Poulsen, K., Schwaeble, W., Sim, R. B., Reid, K. B., Davis, S. J., Thiel, S., and Jensenius, J. C. (2000) Distinct pathways of mannan-binding lectin (MBL)- and C1-complex autoactivation revealed by reconstitution of MBL with recombinant MBLassociated serine protease-2. J. Immunol. 165, 2093-2100 (Pubitemid 30643158)
54. Chen, C. B., and Wallis, R. (2004) Two mechanisms for mannose-binding protein modulation of the activity of its associated serine proteases. J. Biol. Chem. 279, 26058-26065
55. Takahashi, M., Iwaki, D., Kanno, K., Ishida, Y., Xiong, J., Matsushita, M., Endo, Y., Miura, S., Ishii, N., Sugamura, K., and Fujita, T. (2008) Mannose-binding lectin (MBL)-associated serine protease (MASP)-1 contributes to activation of the lectin complement pathway. J. Immunol. 180, 6132-6138
56. Møller-Kristensen, M., Thiel, S., Sjöholm, A., Matsushita, M., and Jensenius, J. C. (2007) Cooperation between MASP-1 and MASP-2 in the generation of C3 convertase through the MBL pathway. Int. Immunol. 19, 141-149 (Pubitemid 46179009)
57. Schwaeble, W. J., Lynch, N. J., Clark, J. E., Marber, M., Samani, N. J., Ali, Y. M., Dudler, T., Parent, B., Lhotta, K., Wallis, R., Farrar, C. A., Sacks, S., Lee, H., Zhang, M., Iwaki, D., Takahashi, M., Fujita, T., Tedford, C. E., and Stover, C. M. (2011) Targeting of mannan-binding lectin-associated serine protease-2 confers protection from myocardial and gastrointestinal ischemia/reperfusion injury. Proc. Natl. Acad. Sci. U.S.A. 108, 7523-7528
58. Qu, H., Magotti, P., Ricklin, D., Wu, E. L., Kourtzelis, I., Wu, Y. Q., Kaznessis, Y. N., and Lambris, J. D. (2011) Novel analogues of the therapeutic complement inhibitor compstatin with significantly improved affinity and potency. Mol. Immunol. 48, 481-489
59. Kadam, A. P., and Sahu, A. (2010) Identification of Complin, a novel complement inhibitor that targets complement proteins factor B and C2. J. Immunol. 184, 7116-7124
60. Roos, A., Nauta, A. J., Broers, D., Faber-Krol, M. C., Trouw, L. A., Drijfhout, J. W., and Daha, M. R. (2001) Specific inhibition of the classical complement pathway by C1q-binding peptides. J. Immunol. 167, 7052-7059 (Pubitemid 33144201)
61. Montalto, M. C., Collard, C. D., Buras, J. A., Reenstra, W. R., McClaine, R., Gies, D. R., Rother, R. P., and Stahl, G. L. (2001) A keratin peptide inhibits mannose-binding lectin. J. Immunol. 166, 4148-4153 (Pubitemid 32224947)
62. Ricklin, D., and Lambris, J. D. (2007) Complement-targeted therapeutics. Nature biotechnology 25, 1265-1275 (Pubitemid 350089828)
63. Volanakis, J. E., and Narayana, S. V. (1996) Complement factor D, a novel serine protease. Protein Sci. 5, 553-564 (Pubitemid 26119490)
64. Milder, F. J., Gomes, L., Schouten, A., Janssen, B. J., Huizinga, E. G., Romijn, R. A., Hemrika, W., Roos, A., Daha, M. R., and Gros, P. (2007) Factor B structure provides insights into activation of the central protease of the complement system. Nat. Struct. Mol. Biol. 14, 224-228 (Pubitemid 46355579)
65. Milder, F. J., Raaijmakers, H. C., Vandeputte, M. D., Schouten, A., Huizinga, E. G., Romijn, R. A., Hemrika, W., Roos, A., Daha, M. R., and Gros, P. (2006) Structure of complement component C2A. Implications for convertase formation and substrate binding. Structure 14, 1587-1597 (Pubitemid 44486814)