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

  • Conference paper
Book cover Cytotoxic Effector Mechanisms

Part of the book series: Current Topics in Microbiology and Immunology ((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).

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Authors and Affiliations

  1. Department of Chemistry and School of Medicine, University of South Carolina, Columbia, SC, 29208, USA

    J. M. Sodetz

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  1. J. M. Sodetz
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Editors and Affiliations

  1. Department of Microbiology and Immunology, University of Miami School of Medicine, P.O. Box 016960(R-138), Miami, FL, 33101, USA

    Eckhard R. Podack M.D.

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© 1988 Springer-Verlag Berlin · Heidelberg

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Sodetz, J.M. (1988). Structure and Function of C8 in the Membrane Attack Sequence of Complement. In: Podack, E.R. (eds) Cytotoxic Effector Mechanisms. Current Topics in Microbiology and Immunology, vol 140. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-73911-8_3

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  • DOI: https://doi.org/10.1007/978-3-642-73911-8_3

  • Publisher Name: Springer, Berlin, Heidelberg

  • Print ISBN: 978-3-642-73913-2

  • Online ISBN: 978-3-642-73911-8

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