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The sequence and topology of human complement component C9.

K K Stanley, H P Kocher, J P Luzio

    The EMBO Journal
    |February 1, 1985
    PubMed
    Summary

    Researchers present a partial nucleotide sequence of human complement component C9 cDNA. This sequence aids in understanding C9 protein structure and function, including its interactions and potential model for topology.

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    Area of Science:

    • Immunology
    • Molecular Biology
    • Protein Chemistry

    Background:

    • The complement system is crucial for innate and adaptive immunity.
    • Complement component C9 is the terminal component of the complement cascade, forming the membrane attack complex (MAC).
    • Understanding C9 structure is vital for elucidating its function in host defense and related pathologies.

    Purpose of the Study:

    • To present a partial nucleotide sequence of human complement component C9 cDNA.
    • To predict the amino acid sequence and analyze structural features of C9.
    • To map monoclonal antibody epitopes and propose a model for C9 topology.

    Main Methods:

    • Nucleotide sequencing of human C9 cDNA.
    • Amino acid sequence prediction from cDNA.

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  • Analysis of protein fragments and Western blotting.
  • Epitope mapping using monoclonal antibodies.

    • Main Results:

    • A partial nucleotide sequence representing 94% of mature human C9 protein was obtained.
    • Predicted amino acid sequence aligns with experimental data from proteolytic fragments.
    • No long hydrophobic stretches were identified, even in the lipid-interacting region.
    • Epitopes were mapped to specific regions, some overlapping with cleavage sites and glycosylation.
    • The N-terminal half shows high homology to LDL receptor cysteine-rich domains.

    Conclusions:

    • The findings provide insights into the primary structure and potential topology of human C9.
    • Structural features suggest specific functional domains within the C9 molecule.
    • A proposed model for C9 topology integrates sequence data, antibody binding, and functional sites.