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Membrane attack by complement.

E R Podack, J Tschopp

    Molecular Immunology
    |July 1, 1984
    PubMed
    Summary
    This summary is machine-generated.

    The complement system forms membrane attack complexes by assembling proteins into a tubular structure. This process involves protein unfolding and polymerization, creating channels that damage cell membranes.

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    Area of Science:

    • Immunology
    • Molecular Biology
    • Biochemistry

    Background:

    • The complement system is crucial for innate and adaptive immunity.
    • Membrane attack complex (MAC) formation is a key effector function of complement.
    • Understanding MAC assembly is vital for comprehending host defense and pathology.

    Purpose of the Study:

    • To elucidate the molecular mechanisms of membrane attack complex assembly.
    • To investigate the protein-protein interactions driving complement-mediated membrane damage.
    • To detail the role of C9 polymerization in channel formation.

    Main Methods:

    • Analysis of protein-protein interactions during complement activation.
    • Structural studies of complement protein complexes.

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  • Biophysical characterization of protein conformational changes.

    • Main Results:

    • Five complement proteins (C5b-C9) self-assemble on target membranes.
    • Hydrophilic precursor proteins undergo restricted unfolding to expose hydrophobic domains.
    • High-affinity interactions drive amphiphilic complex formation.
    • Circular polymerization of C9 (poly C9) forms the transmembrane channel.

    Conclusions:

    • The assembly of the membrane attack complex is a multi-step process involving protein conformational changes and interactions.
    • Transmembrane channel formation is mediated by the circular polymerization of C9.
    • This mechanism underlies complement-mediated cell lysis and membrane lesion formation.