Skip to main content
PMC home page
The Journal of Cell Biology logoLink to The Journal of Cell Biology
. 1982 Sep 1;94(3):755–759. doi: 10.1083/jcb.94.3.755

Terminal membrane C5b-9 complex of human complement: transition from an amphiphilic to a hydrophilic state through binding of the S protein from serum

PMCID: PMC2112234  PMID: 7130282

Abstract

The membrane-damaging C5b-9(m) complex of complement is a cylindrically structured, amphiphilic molecule that is generated on a target membrane during complement attack. Isolated C5b-9(m) complexes are shown here to possess the capacity of binding a protein, termed "S"-protein, that is present in human plasma. Binding of this protein apparently shields the apolar surfaces of C5b-9(m), since the resulting "SC5b-9(m)" complex is hydrophilic and no longer aggregates in detergentfree solution. Dispersed SC5b-9(m) complexes exhibit an apparent sedimentation coefficient of 29S in sucrose density gradients, corresponding to a molecular weight of approximately 1.4 million. SDS PAGE analyses indicate binding of 3-4 molecules of S-protein per C5b-9(m) complex. These data are consistent with a monomer nature and molecular weight of 1-1.1 million of the C5b-9(m) complex. Ultrastructural analysis of SC5b- 9(m) shows preservation of the hollow cylindrical C5b-9(m) structure. Additional material, probably representing the S-protein itself, can be visualized attached to the originally membrane-embedded portion of the macromolecule. The topography of apolar surfaces on a molecule thus appears directly probed and visualized through the binding of a serum protein.

Full Text

The Full Text of this article is available as a PDF (1.5 MB).

Selected References

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

  1. Bhakdi S., Bhakdi-Lehnen B., Tranum-Jensen J. Proteolytic transformation of SC5b-9 into an amphiphilic macromolecule resembling the C5b-9 membrane attack complex of complement. Immunology. 1979 Aug;37(4):901–912. [PMC free article] [PubMed] [Google Scholar]
  2. Bhakdi S., Bjerrum O. J., Bhakdi-Lehnen B., Tranum-Jensen J. Complement lysis: evidence for an amphiphilic nature of the terminal membrane C5b-9 complex of human complement. J Immunol. 1978 Dec;121(6):2526–2532. [PubMed] [Google Scholar]
  3. Bhakdi S., Bjerrum O. J., Rother U., Knüfermann H., Wallach D. F. Immunochemical analyses of membrane-bound complement. Detection of the terminal complement complex and its similarity to "intrinsic" erythrocyte membrane proteins. Biochim Biophys Acta. 1975 Sep 16;406(1):21–35. doi: 10.1016/0005-2736(75)90039-5. [DOI] [PubMed] [Google Scholar]
  4. Bhakdi S., Ey P., Bhakdi-Lehnen B. Isolation of the terminal complement complex from target sheep erythrocyte membranes. Biochim Biophys Acta. 1976 Feb 6;419(3):445–457. doi: 10.1016/0005-2736(76)90258-3. [DOI] [PubMed] [Google Scholar]
  5. Bhakdi S., Roth M. Fluid-phase SC5b-8 complex of human complement: generation and isolation from serum. J Immunol. 1981 Aug;127(2):576–580. [PubMed] [Google Scholar]
  6. Bhakdi S., Tranum-Jensen J. Evidence for a two-domain structure of the terminal membrane C5b-9 complex of human complement. Proc Natl Acad Sci U S A. 1979 Nov;76(11):5872–5876. doi: 10.1073/pnas.76.11.5872. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Bhakdi S., Tranum-Jensen J., Klump O. The terminal membrane C5b-9 complex of human complement. Evidence for the existence of multiple protease-resistant polypeptides that form the trans-membrane complement channel. J Immunol. 1980 May;124(5):2451–2457. [PubMed] [Google Scholar]
  8. Bhakdi S., Tranum-Jensen J. Molecular nature of the complement lesion. Proc Natl Acad Sci U S A. 1978 Nov;75(11):5655–5659. doi: 10.1073/pnas.75.11.5655. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Bhakdi S., Tranum-Jensen J. Molecular weight of the membrane C5b-9 complex of human complement: characterization of the terminal complex as a C5b-9 monomer. Proc Natl Acad Sci U S A. 1981 Mar;78(3):1818–1822. doi: 10.1073/pnas.78.3.1818. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Bhakdi S., Tranum-Jensen J. Re-incorporation of the terminal C5b-9 complement complex into lipid bilayers: formation and stability of reconstituted liposomes. Immunology. 1980 Nov;41(3):737–742. [PMC free article] [PubMed] [Google Scholar]
  11. Biesecker G., Podack E. R., Halverson C. A., Müller-Eberhard H. J. C5b-9 dimer: isolation from complement lysed cells and ultrastructural identification with complement-dependent membrane lesions. J Exp Med. 1979 Feb 1;149(2):448–458. doi: 10.1084/jem.149.2.448. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Bretscher M. S., Raff M. C. Mammalian plasma membranes. Nature. 1975 Nov 6;258(5530):43–49. doi: 10.1038/258043a0. [DOI] [PubMed] [Google Scholar]
  13. Hammer C. H., Nicholson A., Mayer M. M. On the mechanism of cytolysis by complement: evidence on insertion of C5b and C7 subunits of the C5b,6,7 complex into phospholipid bilayers of erythrocyte membranes. Proc Natl Acad Sci U S A. 1975 Dec;72(12):5076–5080. doi: 10.1073/pnas.72.12.5076. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Kolb W. P., Haxby J. A., Arroyave C. M., Müller-Eberhard H. J. Molecular analysis of the membrane attack mechanism of complement. J Exp Med. 1972 Mar 1;135(3):549–566. doi: 10.1084/jem.135.3.549. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Kolb W. P., Muller-Eberhard H. J. The membrane attack mechanism of complement. Isolation and subunit composition of the C5b-9 complex. J Exp Med. 1975 Apr 1;141(4):724–735. [PMC free article] [PubMed] [Google Scholar]
  16. Lachmann P. J., Thompson R. A. Reactive lysis: the complement-mediated lysis of unsensitized cells. II. The characterization of activated reactor as C56 and the participation of C8 and C9. J Exp Med. 1970 Apr 1;131(4):643–657. doi: 10.1084/jem.131.4.643. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Mayer M. M. Complement, past and present. Harvey Lect. 1978;72:139–193. [PubMed] [Google Scholar]
  18. Mayer M. M. Mechanism of cytolysis by complement. Proc Natl Acad Sci U S A. 1972 Oct;69(10):2954–2958. doi: 10.1073/pnas.69.10.2954. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Michaels D. W., Abramovitz A. S., Hammer C. H., Mayer M. M. Increased ion permeability of planar lipid bilayer membranes after treatment with the C5b-9 cytolytic attack mechanism of complement. Proc Natl Acad Sci U S A. 1976 Aug;73(8):2852–2856. doi: 10.1073/pnas.73.8.2852. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Platts-Mills T. A., Ishizaka K. Activation of the alternate pathway of human complements by rabbit cells. J Immunol. 1974 Jul;113(1):348–358. [PubMed] [Google Scholar]
  21. Podack E. R., Müller-Eberhard H. J. Binding of desoxycholate, phosphatidylcholine vesicles, lipoprotein and of the S-protein to complexes of terminal complement components. J Immunol. 1978 Sep;121(3):1025–1030. [PubMed] [Google Scholar]
  22. Podack E. R., Müller-Eberhard H. J. Membrane attack complex of complement. Evidence for its dimeric structure based on hybrid formation. J Biol Chem. 1981 Apr 10;256(7):3145–3148. [PubMed] [Google Scholar]
  23. Podack E. R., Müller-Eberhard H. J. SC5b-9 complex of complement: formation of the dimeric membrane attack complex by removal of S-protein. J Immunol. 1980 Apr;124(4):1779–1783. [PubMed] [Google Scholar]
  24. Singer S. J., Nicolson G. L. The fluid mosaic model of the structure of cell membranes. Science. 1972 Feb 18;175(4023):720–731. doi: 10.1126/science.175.4023.720. [DOI] [PubMed] [Google Scholar]
  25. Thompson R. A., Lachmann P. J. Reactive lysis: the complement-mediated lysis of unsensitized cells. I. The characterization of the indicator factor and its identification as C7. J Exp Med. 1970 Apr 1;131(4):629–641. doi: 10.1084/jem.131.4.629. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Ware C. F., Kolb W. P. Assembly of the functional membrane attack complex of human complement: formation of disulfide-linked C9 dimers. Proc Natl Acad Sci U S A. 1981 Oct;78(10):6426–6430. doi: 10.1073/pnas.78.10.6426. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Ware C. F., Wetsel R. A., Kolb W. P. Physicochemical characterization of fluid phase (SC5b-9) and membrane derived (MC5b-9) attack complexes of human complement purified by immunoadsorbent affinity chromatography or selective detergent extraction. Mol Immunol. 1981 Jun;18(6):521–531. doi: 10.1016/0161-5890(81)90130-9. [DOI] [PubMed] [Google Scholar]

Articles from The Journal of Cell Biology are provided here courtesy of The Rockefeller University Press

RESOURCES