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Related Experiment Videos

Common evolutionary origin of alpha 2-macroglobulin and complement components C3 and C4.

L Sottrup-Jensen, T M Stepanik, T Kristensen

    Proceedings of the National Academy of Sciences of the United States of America
    |January 1, 1985
    PubMed
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    Human alpha-2-macroglobulin (alpha 2M) and complement proteins C3 and C4 share sequence similarities, suggesting a common evolutionary origin. These homologous proteins possess distinct structural domains and functional differences.

    Area of Science:

    • Biochemistry
    • Molecular Biology
    • Evolutionary Biology

    Background:

    • Alpha-2-macroglobulin (alpha 2M) is a large plasma protein involved in immune regulation.
    • Complement components C3 and C4 are key proteins in the complement system, crucial for innate immunity.

    Purpose of the Study:

    • To investigate the evolutionary relationship between alpha 2M and complement proteins C3 and C4.
    • To identify sequence similarities and structural domains shared among these proteins.

    Main Methods:

    • Comparative sequence analysis of human alpha 2M and murine pro-C3.
    • Examination of published sequence data for human complement component C4.

    Main Results:

    • Eight extended regions of sequence similarity were identified between alpha 2M and pro-C3, with 19-31% identical residues.

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  • Significant sequence matches were also observed between alpha 2M, pro-C3, and C4, indicating homology.
  • Structural domains were inferred, suggesting modifications to a common underlying structure.

    • Conclusions:

    • Alpha 2M, C3, and C4 are proposed to be homologous proteins with a common evolutionary origin due to shared sequence similarities and the presence of a unique thiol ester.
    • Differences in specific residues and structural extensions highlight functional divergences among these proteins.