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Related Experiment Videos

The reaction between the complement subcomponent C1q, IgG complexes and polyionic molecules.

N C Hughes-Jones, B Gardner

    Immunology
    |March 1, 1978
    PubMed
    Summary
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    The complement protein C1q binds differently to immune complexes and small molecules. Larger molecules and immune complexes show much stronger binding to C1q, suggesting multiple binding sites are involved.

    Area of Science:

    • Immunology
    • Biochemistry
    • Molecular Biology

    Background:

    • The complement system plays a crucial role in innate and adaptive immunity.
    • C1q is the initiating molecule of the classical complement pathway.
    • Understanding C1q binding is vital for comprehending immune complex clearance and inflammatory responses.

    Purpose of the Study:

    • To investigate the binding affinity of C1q to various ligands.
    • To compare the binding characteristics of C1q with small molecules versus large immune complexes.
    • To elucidate the structural basis for differential C1q binding.

    Main Methods:

    • Utilized 125I-labelled C1q for binding assays.
    • Investigated binding to Fc fragments, small ( < 10,000 MW) and large ( > 100,000 MW) molecular weight polyions (dextran sulfate, polyglutamic acid, polylysine), and immune complexes.

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  • Determined functional affinity constants (Ko).

    • Main Results:

    • C1q exhibited lower affinity (Ko: 0.2–1.5 x 10^4 M^-1) for Fc fragments and small molecular weight polyions.
    • Significantly higher affinity (Ko: 3 x 10^7–4 x 10^8 M^-1) was observed for immune complexes and large molecular weight polyions.
    • Binding affinity was enhanced by reduced ionic strength and reaction with polyions, indicating involvement of ionic groups.

    Conclusions:

    • Differential binding affinities suggest distinct interaction modes: small molecules likely bind to one C1q head, while large molecules/immune complexes engage two heads.
    • Multiple binding sites (potentially six) exist on C1q for polyions like dextran sulfate.
    • Ionic groups are located near or within C1q binding sites, influencing overall binding strength.