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Structure and Function of C8 in the Membrane Attack Sequence of Complement

  • J. M. Sodetz
Part of the Current Topics in Microbiology and Immunology book series (CT MICROBIOLOGY, volume 140)

Abstract

Complement-mediated cell lysis occurs as a result of interactions between complement proteins C5b, C6, C7, C8, and C9 to produce the membrane attack complex C5b-9 (Müller-Eberhard 1986):
$$ C5b\;\xrightarrow{{C6}}\;C5b - 6\;\xrightarrow{{C7}}\;C5b - 7\xrightarrow{{C8}}\;C5b - 8\;\xrightarrow{{nC9}}\;C5b - 9 $$
Assembly of C5b-9 begins with proteolytic conversion of C5 to C5b by the C5 convertases formed as a consequence of complement activation. Development of a transient binding site for C6 leads to formation of a stable C5b-6 dimer. Subsequent binding of C7 and formation of C5b-7 coincides with the expression of a high-affinity lipid-binding site that mediates a strong but noncovalent interaction between the nascent complex and target membranes. Binding of C8 yields the tetramolecular C5b-8 complex. Although capable of slowly lysing erythrocytes and some nucleated cells, C5b-8 functions primarily as a receptor for C9 and thereby mediates formation of the more lytically effective C5b-9 complex. The number of C9 molecules per complex differs depending on C9 input and conditions of formation. The ultrastructure varies accordingly from what are functional lesions with one or a few C9s to highly organized porelike structures formed by polymerization of as many as 16 C9s per C5b-8. Facts and controversies about the function of C9 and the stoichiometry, structure, and mechanism of action of C5b-9 are summarized in other reports (Podack 1986; Müller-Eberhard 1986; Esser 1987; Stanley, this volume).

Keywords

Membrane Attack Complex Human Complement Derive Amino Acid Sequence Baboon Liver Eighth Component 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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Copyright information

© Springer-Verlag Berlin · Heidelberg 1988

Authors and Affiliations

  • J. M. Sodetz
    • 1
  1. 1.Department of Chemistry and School of MedicineUniversity of South CarolinaColumbiaUSA

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