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. 1975 Sep 1;142(3):760–772. doi: 10.1084/jem.142.3.760

Properdin- and nephritic factor-dependent C3 convertases: requirement of native C3 for enzyme formation and the function of bound C3b as properdin receptor

PMCID: PMC2189914  PMID: 1165475

Abstract

Two complex enzymes were assembled that both converted C3 to C3b, one consisting of activated properdin (P), native C3, proactivator (PA) and proactivator convertase (PAase), and the other of nephritic factor (NF) and the same three cofactors. By maintaining a critical concentration of PAase, the P-C3 convertase and the NF-C3 convertase were shown to function efficiently without formation of the C3b-feedback enzyme. The former two enzymes are distinct from the C3b-dependent C3 convertase in that they utilize native C3 instead of C3b and PA in an apparently uncleaved form. The P- and NF-C3 convertase express maximal activity within approximately 10 min at 37 degrees C and decay with a half-life of 35 min at 37 degrees C, which is in contradistinction to the reported lability of the C3b-feedback enzyme. P- and NF-C3 convertases are inhibited by their product C3b, which may constitute a heretofore unknown control of the alternative pathway. A direct physical interaction of P with native C3 and C3b was demonstrated by agglutination of C3b-bearing erythrocytes and by agglutination inhibition. Bound C3b thus constitutes the only known receptor of P and may fulfill an important localizing function for P and the P-C3 convertase in vivo. Although P and NF form functionally similar enzymes, they act independently of each other and are apparently immunochemically unrelated proteins.

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Selected References

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  1. Bokisch V. A., Müller-Eberhard H. J., Cochrane C. G. Isolation of a fragment (C3a) of the third component of human complement containing anaphylatoxin and chemotactic activity and description of an anaphylatoxin inactivator of human serum. J Exp Med. 1969 May 1;129(5):1109–1130. doi: 10.1084/jem.129.5.1109. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Cooper N. R., Polley M. J., Müller-Eberhard H. J. The second component of human complement (C2): quantitative molecular analysis of its reactions in immune hemolysis. Immunochemistry. 1970 Apr;7(4):341–356. doi: 10.1016/0019-2791(70)90237-5. [DOI] [PubMed] [Google Scholar]
  3. DAVIS B. J. DISC ELECTROPHORESIS. II. METHOD AND APPLICATION TO HUMAN SERUM PROTEINS. Ann N Y Acad Sci. 1964 Dec 28;121:404–427. doi: 10.1111/j.1749-6632.1964.tb14213.x. [DOI] [PubMed] [Google Scholar]
  4. Fearon D. T., Austen K. F., Ruddy S. Formation of a hemolytically active cellular intermediate by the interaction between properdin factors B and D and the activated third component of complement. J Exp Med. 1973 Dec 1;138(6):1305–1313. doi: 10.1084/jem.138.6.1305. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Götze O., Müller-Eberhard H. J. The C3-activator system: an alternate pathway of complement activation. J Exp Med. 1971 Sep 1;134(3 Pt 2):90s–108s. [PubMed] [Google Scholar]
  6. Götze O., Müller-Eberhard H. J. The role of properdin in the alternate pathway of complement activation. J Exp Med. 1974 Jan 1;139(1):44–57. doi: 10.1084/jem.139.1.44. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. March S. C., Parikh I., Cuatrecasas P. A simplified method for cyanogen bromide activation of agarose for affinity chromatography. Anal Biochem. 1974 Jul;60(1):149–152. doi: 10.1016/0003-2697(74)90139-0. [DOI] [PubMed] [Google Scholar]
  8. Minta J. O., Lepow I. H. Studies on the sub-unit structure of human properdin. Immunochemistry. 1974 Jul;11(7):361–368. doi: 10.1016/0019-2791(74)90189-x. [DOI] [PubMed] [Google Scholar]
  9. Müller-Eberhard H. J., Fjellström K. E. Isolation of the anticomplementary protein from cobra venom and its mode of action on C3. J Immunol. 1971 Dec;107(6):1666–1672. [PubMed] [Google Scholar]
  10. Müller-Eberhard H. J., Götze O. C3 proactivator convertase and its mode of action. J Exp Med. 1972 Apr 1;135(4):1003–1008. doi: 10.1084/jem.135.4.1003. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Nicol P. A., Lachmann P. J. The alternate pathway of complement activation. The role of C3 and its inactivator (KAF). Immunology. 1973 Feb;24(2):259–275. [PMC free article] [PubMed] [Google Scholar]
  12. Polley M. J., Müller-Eberhard H. J. Enharncement of the hemolytic activity of the second component of human complement by oxidation. J Exp Med. 1967 Dec 1;126(6):1013–1025. doi: 10.1084/jem.126.6.1013. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Rothfield N., Ross H. A., Minta J. O., Lepow I. H. Glomerular and dermal depostion of properdin in systemic lupus erythematosus. N Engl J Med. 1972 Oct 5;287(14):681–685. doi: 10.1056/NEJM197210052871402. [DOI] [PubMed] [Google Scholar]
  14. Schreiber R. D., Müller-Eberhard H. J. Fourth component of human complement: description of a three polypeptide chain structure. J Exp Med. 1974 Nov 1;140(5):1324–1335. doi: 10.1084/jem.140.5.1324. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Theofilopoulos A. N., Bokisch V. A., Dixon F. J. Receptor for soluble C3 and C3b on human lymphoblastoid (RAJI) cells. Properties and biologocal significance. J Exp Med. 1974 Mar 1;139(3):696–711. doi: 10.1084/jem.139.3.696. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Vallota E. H., Forristal J., Spitzer R. E., Davis N. C., West C. D. Characteristics of a non-complement-dependent C3-reactive complex formed form factors in nephritic and normal serum. J Exp Med. 1970 Jun 1;131(6):1306–1324. doi: 10.1084/jem.131.6.1306. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Vallota E. H., Götze O., Spiegelberg H. L., Forristal J., West C. D., Müller-Eberhard H. J. A serum factor in chronic hypocomplementemic hephritis distinct from immunoglobulins and activating the alternate pathway of complement. J Exp Med. 1974 May 1;139(5):1249–1261. doi: 10.1084/jem.139.5.1249. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Verroust P. J., Wilson C. B., Cooper N. R., Edgington T. S., Dixon F. J. Glomerular complement components in human glomerulonephritis. J Clin Invest. 1974 Jan;53(1):77–84. doi: 10.1172/JCI107562. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Westberg N. G., Naff G. B., Boyer J. T., Michael A. F. Glomerular deposition of properdin in acute and chronic glomerulonephritis with hypocomplementemia. J Clin Invest. 1971 Mar;50(3):642–649. doi: 10.1172/JCI106534. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Williams D. G., Lachmann P. J., Charlesworth J. A., Peters D. K. Role of C3b in the breakdown of C3 in hypocomplementaemic mesangiocapillary glomerulonephritis. Lancet. 1973 Mar 3;1(7801):447–449. doi: 10.1016/s0140-6736(73)91877-1. [DOI] [PubMed] [Google Scholar]
  21. Williams D. G., Peters D. K., Fallows J., Petrie A., Kourilsky O., Morel-Maroger L., Cameron J. S. Studies of serum complement in the hypocomplementaemic nephritides. Clin Exp Immunol. 1974 Nov;18(3):391–405. [PMC free article] [PubMed] [Google Scholar]

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