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Ca(2+)-linked association of human complement C1s and C1r
G Rivas1, K C Ingham, A P Minton
1Laboratory of Biochemical Pharmacology, National Institute of Diabetes and Digestive Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892.
Biochemistry
|March 1, 1994
Summary
Calcium ions significantly influence the interaction between complement subcomponents Clr and Cls. Dimeric Clr binds Cls, with binding affinity increasing 1000-fold as calcium concentration rises, favoring heteroassociation.
Area of Science:
- Biochemistry
- Molecular Biology
- Immunology
Background:
- The complement system is crucial for innate immunity.
- Complement Clr and Cls are serine protease subcomponents of the first component of complement (Cl).
- Calcium ions are known to modulate complement activation.
Purpose of the Study:
- To investigate the heteroassociation between Clr and Cls.
- To quantify the effect of calcium ion concentration on Clr-Cls interactions.
- To develop a quantitative model for Clr-Cls binding.
Main Methods:
- Tracer sedimentation equilibrium was used to measure molecular weight.
- Varying concentrations of Ca2+ and Cls were employed.
- A quantitative model for heteroassociation was fitted to experimental data.
Main Results:
- Clr exists as a dimer under all tested conditions.
- Dimeric Clr can bind up to two molecules of Cls.
- The association constant for Clr-Cls binding increases ~1000-fold with increasing Ca2+ concentration (1 nM to 1.0 mM).
- Heteroassociation of Clr and Cls is favored over Cls self-association.
Conclusions:
- Calcium concentration is a critical factor in regulating Clr-Cls interactions.
- Multiple states of association must be considered for understanding complement component equilibria.
- These findings are essential for elucidating the functional mechanisms of complement Cl activation.