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Monomeric structures of the zymogen and active catalytic domain of complement protease c1r: further insights into the c1 activation mechanism.

Budayova-Spano M, Grabarse W, Thielens NM, Hillen H, Lacroix M, Schmidt M, Fontecilla-Camps JC, Arlaud GJ, Gaboriaud C
Structure 10 1509-19 (2002)
Cited: 41 times
EuropePMC logo PMID: 12429092

Abstract

C1r is the serine protease (SP) that mediates autoactivation of C1, the complex that triggers the classical complement pathway. We have determined the crystal structure of two fragments from the human C1r catalytic domain, each encompassing the second complement control protein (CCP2) module and the SP domain. The wild-type species has an active structure, whereas the S637A mutant is a zymogen. The structures reveal a restricted hinge flexibility of the CCP2-SP interface, and both are characterized by the unique alpha-helical conformation of loop E. The zymogen activation domain exhibits high mobility, and the active structure shows a restricted access to most substrate binding subsites. Further implications relevant to the C1r self-activation process are derived from protein-protein interactions in the crystals.

Reviews - 1md7 mentioned but not cited (1)

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Articles - 1md7 mentioned but not cited (2)

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Reviews citing this publication (13)

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  8. Haptoglobin. Andersen CBF, Stødkilde K, Sæderup KL, Kuhlee A, Raunser S, Graversen JH, Moestrup SK. Antioxid Redox Signal 26 814-831 (2017)
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  2. A true autoactivating enzyme. Structural insight into mannose-binding lectin-associated serine protease-2 activations. Gál P, Harmat V, Kocsis A, Bián T, Barna L, Ambrus G, Végh B, Balczer J, Sim RB, Náray-Szabó G, Závodszky P. J Biol Chem 280 33435-33444 (2005)
  3. Crystal structure of the CUB1-EGF-CUB2 region of mannose-binding protein associated serine protease-2. Feinberg H, Uitdehaag JC, Davies JM, Wallis R, Drickamer K, Weis WI. EMBO J 22 2348-2359 (2003)
  4. Regulation of tumor necrosis factor receptor-1 and the IKK-NF-kappaB pathway by LDL receptor-related protein explains the antiinflammatory activity of this receptor. Gaultier A, Arandjelovic S, Niessen S, Overton CD, Linton MF, Fazio S, Campana WM, Cravatt BF, Gonias SL. Blood 111 5316-5325 (2008)
  5. Structures of C1-IgG1 provide insights into how danger pattern recognition activates complement. Ugurlar D, Howes SC, de Kreuk BJ, Koning RI, de Jong RN, Beurskens FJ, Schuurman J, Koster AJ, Sharp TH, Parren PWHI, Gros P. Science 359 794-797 (2018)
  6. 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. Harmat V, Gál P, Kardos J, Szilágyi K, Ambrus G, Végh B, Náray-Szabó G, Závodszky P. J Mol Biol 342 1533-1546 (2004)
  7. Elucidation of the substrate specificity of the MASP-2 protease of the lectin complement pathway and identification of the enzyme as a major physiological target of the serpin, C1-inhibitor. Kerr FK, Thomas AR, Wijeyewickrema LC, Whisstock JC, Boyd SE, Kaiserman D, Matthews AY, Bird PI, Thielens NM, Rossi V, Pike RN. Mol Immunol 45 670-677 (2008)
  8. Selective inhibition of the lectin pathway of complement with phage display selected peptides against mannose-binding lectin-associated serine protease (MASP)-1 and -2: significant contribution of MASP-1 to lectin pathway activation. Kocsis A, Kékesi KA, Szász R, Végh BM, Balczer J, Dobó J, Závodszky P, Gál P, Pál G. J Immunol 185 4169-4178 (2010)
  9. Crystallographic and kinetic evidence of allostery in a trypsin-like protease. Niu W, Chen Z, Gandhi PS, Vogt AD, Pozzi N, Pelc LA, Zapata F, Di Cera E. Biochemistry 50 6301-6307 (2011)
  10. Revisiting the mechanism of the autoactivation of the complement protease C1r in the C1 complex: structure of the active catalytic region of C1r. Kardos J, Harmat V, Palló A, Barabás O, Szilágyi K, Gráf L, Náray-Szabó G, Goto Y, Závodszky P, Gál P. Mol Immunol 45 1752-1760 (2008)
  11. A molecular switch governs the interaction between the human complement protease C1s and its substrate, complement C4. Perry AJ, Wijeyewickrema LC, Wilmann PG, Gunzburg MJ, D'Andrea L, Irving JA, Pang SS, Duncan RC, Wilce JA, Whisstock JC, Pike RN. J Biol Chem 288 15821-15829 (2013)
  12. Calcium-dependent conformational flexibility of a CUB domain controls activation of the complement serine protease C1r. Major B, Kardos J, Kékesi KA, Lorincz Z, Závodszky P, Gál P. J Biol Chem 285 11863-11869 (2010)
  13. Mapping surface accessibility of the C1r/C1s tetramer by chemical modification and mass spectrometry provides new insights into assembly of the human C1 complex. Brier S, Pflieger D, Le Mignon M, Bally I, Gaboriaud C, Arlaud GJ, Daniel R. J Biol Chem 285 32251-32263 (2010)
  14. Molecular determinants of the substrate specificity of the complement-initiating protease, C1r. Wijeyewickrema LC, Yongqing T, Tran TP, Thompson PE, Viljoen JE, Coetzer TH, Duncan RC, Kass I, Buckle AM, Pike RN. J Biol Chem 288 15571-15580 (2013)
  15. The serine protease domain of MASP-3: enzymatic properties and crystal structure in complex with ecotin. Gaboriaud C, Gupta RK, Martin L, Lacroix M, Serre L, Teillet F, Arlaud GJ, Rossi V, Thielens NM. PLoS One 8 e67962 (2013)
  16. A wealth of genotype-specific proteoforms fine-tunes hemoglobin scavenging by haptoglobin. Tamara S, Franc V, Heck AJR. Proc Natl Acad Sci U S A 117 15554-15564 (2020)
  17. The Structural Basis for Complement Inhibition by Gigastasin, a Protease Inhibitor from the Giant Amazon Leech. Pang SS, Wijeyewickrema LC, Hor L, Tan S, Lameignere E, Conway EM, Blom AM, Mohlin FC, Liu X, Payne RJ, Whisstock JC, Pike RN. J Immunol 199 3883-3891 (2017)
  18. C1R Mutations Trigger Constitutive Complement 1 Activation in Periodontal Ehlers-Danlos Syndrome. Gröbner R, Kapferer-Seebacher I, Amberger A, Redolfi R, Dalonneau F, Björck E, Milnes D, Bally I, Rossi V, Thielens N, Stoiber H, Gaboriaud C, Zschocke J. Front Immunol 10 2537 (2019)
  19. Leishmania donovani Inhibitor of Serine Peptidases 2 Mediated Inhibition of Lectin Pathway and Upregulation of C5aR Signaling Promote Parasite Survival inside Host. Verma S, Mandal A, Ansari MY, Kumar A, Abhishek K, Ghosh AK, Kumar A, Kumar V, Das S, Das P. Front Immunol 9 63 (2018)
  20. Borrelia miyamotoi FbpA and FbpB Are Immunomodulatory Outer Surface Lipoproteins With Distinct Structures and Functions. Booth CE, Powell-Pierce AD, Skare JT, Garcia BL. Front Immunol 13 886733 (2022)
  21. Deconvolving multiplexed protease signatures with substrate reduction and activity clustering. Zhuang Q, Holt BA, Kwong GA, Qiu P. PLoS Comput Biol 15 e1006909 (2019)
  22. A Structural Basis for Inhibition of the Complement Initiator Protease C1r by Lyme Disease Spirochetes. Garrigues RJ, Powell-Pierce AD, Hammel M, Skare JT, Garcia BL. J Immunol 207 2856-2867 (2021)
  23. HMGB1 cleavage by complement C1s and its potent anti-inflammatory product. Lorvellec M, Chouquet A, Koch J, Bally I, Signor L, Vigne J, Dalonneau F, Thielens NM, Rabilloud T, Dalzon B, Rossi V, Gaboriaud C. Front Immunol 14 1151731 (2023)
  24. Structural model of haptoglobin and its complex with the anticoagulant ecotin variants: structure-activity relationship study and analysis of interactions. Sathler PC, Lourenço AL, Miceli LA, Rodrigues CR, Albuquerque MG, Cabral LM, Castro HC. J Enzyme Inhib Med Chem 29 256-262 (2014)
  25. Targeting the Initiator Protease of the Classical Pathway of Complement Using Fragment-Based Drug Discovery. Rushing BR, Rohlik DL, Roy S, Skaff DA, Garcia BL. Molecules 25 (2020)


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