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Human complement component C3: cDNA coding sequence and derived primary structure.

M H de Bruijn, G H Fey

    Proceedings of the National Academy of Sciences of the United States of America
    |February 1, 1985
    PubMed
    Summary
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    Researchers present the human complement component C3 (C3) sequence, detailing its structure and functional sites. This analysis reveals evolutionary links between C3, C4, and alpha-2-macroglobulin, enhancing our understanding of the complement system.

    Area of Science:

    • Biochemistry
    • Immunology
    • Molecular Biology

    Background:

    • The complement system is crucial for innate immunity.
    • Complement component C3 (C3) is a central protein in complement activation.
    • Understanding C3 structure and function is vital for immunology research.

    Purpose of the Study:

    • To present the complete cDNA coding sequence and derived amino acid sequence of human C3.
    • To identify and localize functionally important sites within the human C3 protein.
    • To investigate the evolutionary relationship of human C3 with related proteins.

    Main Methods:

    • cDNA sequencing
    • Amino acid sequence analysis
    • Bioinformatic comparison with homologous proteins

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    Main Results:

    • The complete human C3 precursor sequence, including signal peptide, beta chain, and alpha chain, was determined.
    • Key functional sites (thiolester, anaphylatoxin cleavage, Factor I cleavage, leukocyte mobilization) were localized.
    • Human C3 exhibits significant sequence identity (79% nucleotide, 77% amino acid) with mouse C3.
    • Homology was observed between C3, alpha-2-macroglobulin, and C4, suggesting common ancestry.

    Conclusions:

    • The detailed sequence and functional site mapping provide a comprehensive resource for C3 research.
    • Identified functional sites are critical for C3's role in the complement cascade.
    • Sequence homology supports an evolutionary link between C3, C4, and alpha-2-macroglobulin, shedding light on protein evolution within the immune system.