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Related Experiment Videos

The killer molecule of complement.

H J Müller-Eberhard

    The Journal of Investigative Dermatology
    |July 1, 1985
    PubMed
    Summary
    This summary is machine-generated.

    The membrane attack complex (MAC) causes cell injury via complement activation. This complex, formed by proteins C5-C9, creates a pore in cell membranes, leading to cell damage.

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    Area of Science:

    • Immunology
    • Molecular Biology
    • Cell Biology

    Background:

    • Cell injury is mediated by the complement system's membrane attack complex (MAC).
    • The MAC is assembled from precursor proteins C5, C6, C7, C8, and C9.
    • Activation occurs through classical or alternative complement pathways on cell surfaces.

    Purpose of the Study:

    • To elucidate the assembly process and structural characteristics of the membrane attack complex (MAC).
    • To understand the molecular transitions and functional pore formation by the MAC.
    • To identify regulatory mechanisms controlling MAC formation and cell membrane interaction.

    Main Methods:

    • Analysis of complement protein interactions and complex formation (C5-C9).
    • Investigation of hydrophilic-amphiphilic transitions during MAC assembly.

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  • Characterization of C9 polymerization and its role in pore formation.
  • Examination of regulatory proteins like S-protein and species-specific membrane proteins.
  • Main Results:

    • The MAC assembly involves sequential binding of C5b, C6, C7, C8, and C9, forming a pore with a maximal diameter of approximately 100 Å.
    • C9 polymerization is a critical step, involving unfolding and lateral association of monomers to form a tubular structure.
    • The C-terminal portion of C9 mediates phospholipid binding and membrane insertion.
    • Regulatory proteins, including S-protein and specific membrane proteins, control MAC formation and cell attachment.

    Conclusions:

    • The MAC forms a functional transmembrane channel through a complex polymerization process of C9.
    • Understanding MAC assembly and regulation is crucial for comprehending complement-mediated cell injury.
    • Regulatory mechanisms involving S-protein and membrane proteins prevent uncontrolled MAC formation and cell damage.