Skip to main content
The Journal of Experimental Medicine logoLink to The Journal of Experimental Medicine
. 1984 Jan 1;159(1):324–329. doi: 10.1084/jem.159.1.324

MHC Class III products: an electron microscopic study of the C3 convertases of human complement

PMCID: PMC2187187  PMID: 6559206

Abstract

We have reported a transmission electron microscopic study of the two C3 convertases of human complement and their precursors. The corresponding proteins and complexes of the classical and alternative pathway appear very similar. Cofactors C3b and C4b are nearly indistinguishable and display a characteristic but highly irregular substructure. C2 and Factor B are globular with diameters of 85 +/- 8 A and 80 +/- 8 A and both consist of three discrete globular domains each approximately 40 A in diameter. Bb and C2a each contain two domains connected by a short linker segment. Both domains of Bb and one domain of C2a are 42 A in diameter (28 kd), while the second domain of C2 is 47 A in diameter (39 kd). Attachment of the enzymatic subunits to cofactors occurs through one domain only.

Full Text

The Full Text of this article is available as a PDF (1.1 MB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Campbell R. D., Gagnon J., Porter R. R. Amino acid sequence around the proposed thiolester bond of human complement component C4 and comparison with the corresponding sequences from C3 and alpha 2-macroglobulin. Biosci Rep. 1981 May;1(5):423–429. doi: 10.1007/BF01116192. [DOI] [PubMed] [Google Scholar]
  2. Campbell R. D., Porter R. R. Molecular cloning and characterization of the gene coding for human complement protein factor B. Proc Natl Acad Sci U S A. 1983 Jul;80(14):4464–4468. doi: 10.1073/pnas.80.14.4464. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Curman B., Sandberg-Trägårdh L., Peterson P. A. Chemical characterization of human factor B of the alternate pathway of complement activation. Biochemistry. 1977 Nov 29;16(24):5368–5375. doi: 10.1021/bi00643a031. [DOI] [PubMed] [Google Scholar]
  4. Fearon D. T. Regulation of the amplification C3 convertase of human complement by an inhibitory protein isolated from human erythrocyte membrane. Proc Natl Acad Sci U S A. 1979 Nov;76(11):5867–5871. doi: 10.1073/pnas.76.11.5867. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Kerr M. A. Limited proteolysis of complement components C2 and factor B. Structural analogy and limited sequence homology. Biochem J. 1979 Dec 1;183(3):615–622. doi: 10.1042/bj1830615. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Laemmli U. K. Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature. 1970 Aug 15;227(5259):680–685. doi: 10.1038/227680a0. [DOI] [PubMed] [Google Scholar]
  7. Law S. K., Levine R. P. Interaction between the third complement protein and cell surface macromolecules. Proc Natl Acad Sci U S A. 1977 Jul;74(7):2701–2705. doi: 10.1073/pnas.74.7.2701. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Moon K. E., Gorski J. P., Hugli T. E. Complete primary structure of human C4a anaphylatoxin. J Biol Chem. 1981 Aug 25;256(16):8685–8692. [PubMed] [Google Scholar]
  9. Müller-Eberhard H. J., Schreiber R. D. Molecular biology and chemistry of the alternative pathway of complement. Adv Immunol. 1980;29:1–53. doi: 10.1016/s0065-2776(08)60042-5. [DOI] [PubMed] [Google Scholar]
  10. Niemann M. A., Volanakis J. E., Mole J. E. Amino-terminal sequence of human factor B of the alternative complement pathway and its cleavage fragments, Ba and Bb. Biochemistry. 1980 Apr 15;19(8):1576–1583. doi: 10.1021/bi00549a007. [DOI] [PubMed] [Google Scholar]
  11. Pangburn M. K., Müller-Eberhard H. J. Kinetic and thermodynamic analysis of the control of C3b by the complement regulatory proteins factors H and I. Biochemistry. 1983 Jan 4;22(1):178–185. doi: 10.1021/bi00270a026. [DOI] [PubMed] [Google Scholar]
  12. Pangburn M. K., Müller-Eberhard H. J. Relation of putative thioester bond in C3 to activation of the alternative pathway and the binding of C3b to biological targets of complement. J Exp Med. 1980 Oct 1;152(4):1102–1114. doi: 10.1084/jem.152.4.1102. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Pangburn M. K., Schreiber R. D., Müller-Eberhard H. J. 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. 1977 Jul 1;146(1):257–270. doi: 10.1084/jem.146.1.257. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Polley M. J., Müller-Eberhard H. J. The second component of human complement: its isolation, fragmentation by C'1 esterase, and incorporation into C'3 convertase. J Exp Med. 1968 Sep 1;128(3):533–551. doi: 10.1084/jem.128.3.533. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Reid K. B., Porter R. R. The proteolytic activation systems of complement. Annu Rev Biochem. 1981;50:433–464. doi: 10.1146/annurev.bi.50.070181.002245. [DOI] [PubMed] [Google Scholar]
  16. 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]
  17. Seegan G. W., Smith C. A., Schumaker V. N. Changes in quaternary structure of IgG upon reduction of the interheavy-chain disulfide bond. Proc Natl Acad Sci U S A. 1979 Feb;76(2):907–911. doi: 10.1073/pnas.76.2.907. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Smith C. A., Vogel C. W., Müller-Eberhard H. J. Ultrastructure of cobra venom factor-dependent C3/C5 convertase and its zymogen, factor B of human complement. J Biol Chem. 1982 Sep 10;257(17):9879–9882. [PubMed] [Google Scholar]
  19. Tack B. F., Harrison R. A., Janatova J., Thomas M. L., Prahl J. W. Evidence for presence of an internal thiolester bond in third component of human complement. Proc Natl Acad Sci U S A. 1980 Oct;77(10):5764–5768. doi: 10.1073/pnas.77.10.5764. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Vogel C. W., Müller-Eberhard H. J. The cobra venom factor-dependent C3 convertase of human complement. A kinetic and thermodynamic analysis of a protease acting on its natural high molecular weight substrate. J Biol Chem. 1982 Jul 25;257(14):8292–8299. [PubMed] [Google Scholar]
  21. Watson H. C., Shotton D. M., Cox J. M., Muirhead H. Three-dimensional Fourier synthesis of tosyl-elastase at 3.5 å resolution. Nature. 1970 Feb 28;225(5235):806–811. doi: 10.1038/225806a0. [DOI] [PubMed] [Google Scholar]
  22. Whitehead A. S., Solomon E., Chambers S., Bodmer W. F., Povey S., Fey G. Assignment of the structural gene for the third component of human complement to chromosome 19. Proc Natl Acad Sci U S A. 1982 Aug;79(16):5021–5025. doi: 10.1073/pnas.79.16.5021. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Wright H. T. Comparison of the crystal structures of chymotrypsinogen-A and alpha-chymotrypsin. J Mol Biol. 1973 Sep 5;79(1):1–11. doi: 10.1016/0022-2836(73)90265-9. [DOI] [PubMed] [Google Scholar]

Articles from The Journal of Experimental Medicine are provided here courtesy of The Rockefeller University Press

RESOURCES