complement c3 c5 convertases

Summary

Summary: Serine proteases that cleave COMPLEMENT C3 into COMPLEMENT C3A and COMPLEMENT C3B, or cleave COMPLEMENT C5 into COMPLEMENT C5A and COMPLEMENT C5B. These include the different forms of C3/C5 convertases in the classical and the alternative pathways of COMPLEMENT ACTIVATION. Both cleavages take place at the C-terminal of an ARGININE residue.

Top Publications

  1. Janssen B, Gomes L, Koning R, Svergun D, Koster A, Fritzinger D, et al. Insights into complement convertase formation based on the structure of the factor B-cobra venom factor complex. EMBO J. 2009;28:2469-78 pubmed publisher
    ..These insights into formation of convertases provide a basis for further development of complement therapeutics. ..
  2. Li Q, Nacion K, Bu H, Lin F. The complement inhibitor FUT-175 suppresses T cell autoreactivity in experimental autoimmune encephalomyelitis. Am J Pathol. 2009;175:661-7 pubmed publisher
    ..These results argue that complement regulators, which inhibit C5a/C3a production, may have therapeutic efficacy in multiple sclerosis and in other clinical conditions in which T cells drive disease pathogenesis. ..
  3. Adra A, Vigue M, Dalla Vale F, Ichay L, Raynaud P, Mariani A, et al. Favorable outcome in a case of Mycoplasma pneumoniae-associated crescentic glomerulonephritis. Pediatr Nephrol. 2010;25:1765-9 pubmed publisher
    ..This treatment regimen led to disease remission and a favorable renal outcome at the 6-month follow-up. However, the treatment guidelines in this situation remain debatable. ..
  4. Liszewski M, Bertram P, Leung M, Hauhart R, Zhang L, Atkinson J. Smallpox inhibitor of complement enzymes (SPICE): regulation of complement activation on cells and mechanism of its cellular attachment. J Immunol. 2008;181:4199-207 pubmed
    ..These results provide insights related to the complement inhibitory activities of poxviral inhibitors of complement and describe a mAb with therapeutic potential. ..
  5. Reuter M, Caswell C, Lukomski S, Zipfel P. Binding of the human complement regulators CFHR1 and factor H by streptococcal collagen-like protein 1 (Scl1) via their conserved C termini allows control of the complement cascade at multiple levels. J Biol Chem. 2010;285:38473-85 pubmed publisher
  6. Raedler H, Yang M, Lalli P, Medof M, Heeger P. Primed CD8(+) T-cell responses to allogeneic endothelial cells are controlled by local complement activation. Am J Transplant. 2009;9:1784-95 pubmed publisher
    ..The findings reveal that EC-derived complement triggers secondary CD8 T-cell differentiation and expansion and argue that targeting complement and/or C5aR could limit T-cell-mediated graft injury. ..
  7. Rawal N, Rajagopalan R, Salvi V. Stringent regulation of complement lectin pathway C3/C5 convertase by C4b-binding protein (C4BP). Mol Immunol. 2009;46:2902-10 pubmed publisher
  8. Avirutnan P, Fuchs A, Hauhart R, Somnuke P, Youn S, Diamond M, et al. Antagonism of the complement component C4 by flavivirus nonstructural protein NS1. J Exp Med. 2010;207:793-806 pubmed publisher
    ..Through this mechanism, NS1 protects DENV from complement-dependent neutralization in solution. These studies define a novel immune evasion mechanism for restricting complement control of microbial infection...
  9. Jongerius I, Garcia B, Geisbrecht B, Van Strijp J, Rooijakkers S. Convertase inhibitory properties of Staphylococcal extracellular complement-binding protein. J Biol Chem. 2010;285:14973-9 pubmed publisher
    ..Here, we show that binding of Ecb to the C3d domain of C3b is crucial for inhibition of C5 convertases. Ecb does not interfere with substrate binding to convertases but prevents formation of an active convertase enzyme. ..

More Information

Publications23

  1. Boxx G, Nishiya C, Kozel T, Zhang M. Characteristics of Fc-independent human antimannan antibody-mediated alternative pathway initiation of C3 deposition to Candida albicans. Mol Immunol. 2009;46:473-80 pubmed publisher
    ..Thus, human antimannan antibody has a distinct Fc-independent effector function in regulation of C3 deposition to C. albicans. ..
  2. Chen H, Ricklin D, Hammel M, Garcia B, McWhorter W, Sfyroera G, et al. Allosteric inhibition of complement function by a staphylococcal immune evasion protein. Proc Natl Acad Sci U S A. 2010;107:17621-6 pubmed publisher
    ..As this enzyme complex is critical for both activation and amplification of the complement response, its allosteric inhibition likely represents a fundamental contribution to the overall immune evasion strategy of S. aureus. ..
  3. Martinez Barricarte R, Heurich M, Valdes Cañedo F, Vazquez Martul E, Torreira E, Montes T, et al. Human C3 mutation reveals a mechanism of dense deposit disease pathogenesis and provides insights into complement activation and regulation. J Clin Invest. 2010;120:3702-12 pubmed publisher
  4. Luo S, Hartmann A, Dahse H, Skerka C, Zipfel P. Secreted pH-regulated antigen 1 of Candida albicans blocks activation and conversion of complement C3. J Immunol. 2010;185:2164-73 pubmed publisher
    ..Thus, Pra1 is, to our knowledge, the first potent fungal complement inhibitor that favors C. albicans immune escape by inactivating and controlling host complement attack at the level of C3...
  5. Serkova N, Renner B, Larsen B, Stoldt C, Hasebroock K, Bradshaw Pierce E, et al. Renal inflammation: targeted iron oxide nanoparticles for molecular MR imaging in mice. Radiology. 2010;255:517-26 pubmed publisher
    ..Injection of CR2-conjugated SPIO caused a significant reduction in T2-weighted MR imaging signal and T2 relaxation time in nephritic kidneys. ..
  6. Hoedemaekers C, van Deuren M, Sprong T, Pickkers P, Mollnes T, Klasen I, et al. The complement system is activated in a biphasic pattern after coronary artery bypass grafting. Ann Thorac Surg. 2010;89:710-6 pubmed publisher
    ..Complement activation after cardiac surgery is regulated in a complex biphasic way, with additional inhibitory mechanisms engaged from 8 hours postoperatively onward. ..
  7. Roumenina L, Jablonski M, Hue C, Blouin J, Dimitrov J, Dragon Durey M, et al. Hyperfunctional C3 convertase leads to complement deposition on endothelial cells and contributes to atypical hemolytic uremic syndrome. Blood. 2009;114:2837-45 pubmed publisher
    ..Therefore, risk factors for aHUS are not only mutations leading to loss of regulation, but also mutations, resulting in hyperactive C3 convertase. ..
  8. Rooijakkers S, Wu J, Ruyken M, van Domselaar R, Planken K, Tzekou A, et al. Structural and functional implications of the alternative complement pathway C3 convertase stabilized by a staphylococcal inhibitor. Nat Immunol. 2009;10:721-7 pubmed publisher
    ..Understanding the mechanistic basis of the central complement-activation step and microbial immune evasion strategies targeting this step will aid in the development of complement therapeutics. ..
  9. Krishnan V, Ponnuraj K, Xu Y, Macon K, Volanakis J, Narayana S. The crystal structure of cobra venom factor, a cofactor for C3- and C5-convertase CVFBb. Structure. 2009;17:611-9 pubmed publisher
    ..The similarly positioned CUB and slightly displaced C345c domains of CVF could play a vital role in the formation of C3 convertases by providing important primary binding sites for factor B. ..
  10. Jongerius I, Puister M, Wu J, Ruyken M, Van Strijp J, Rooijakkers S. Staphylococcal complement inhibitor modulates phagocyte responses by dimerization of convertases. J Immunol. 2010;184:420-5 pubmed publisher
    ..The dimerization site of SCIN is essential for its strong antiphagocytic properties. These studies provide critical insights into the unique immune-evasion strategies used by S. aureus. ..
  11. Zipfel P, Skerka C. Complement regulators and inhibitory proteins. Nat Rev Immunol. 2009;9:729-40 pubmed publisher
    ..Therefore, insights into the mechanisms of complement regulation are crucial for understanding disease pathology and for enabling the development of diagnostic tools and therapies for complement-associated diseases. ..
  12. Halili M, Ruiz Gómez G, Le G, Abbenante G, Fairlie D. Complement component C2, inhibiting a latent serine protease in the classical pathway of complement activation. Biochemistry. 2009;48:8466-72 pubmed publisher
    ..These results provide a new avenue and valuable new insights to inhibiting CP complement activation relevant to inflammatory diseases. ..
  13. PEAKE P, Shen Y. Factor H binds to the N-terminus of adiponectin and modulates complement activation. Biochem Biophys Res Commun. 2010;397:361-6 pubmed publisher
  14. Heinen S, Hartmann A, Lauer N, Wiehl U, Dahse H, Schirmer S, et al. Factor H-related protein 1 (CFHR-1) inhibits complement C5 convertase activity and terminal complex formation. Blood. 2009;114:2439-47 pubmed publisher
    ..These findings provide new insights into complement regulation on the cell surface and biosurfaces and likely define the role of CFHR1 in human diseases. ..