Related Experiment Videos
Association of terminal complement proteins in solution and modulation by suramin.
C Saez1, N M Thielens, E S Bjes
1Division of Cell Biology and Biophysics, School of Biological Sciences, University of Missouri-Kansas City 64110, USA.
Biochemistry
|May 29, 1999
Summary
The complement system proteins C8 and C9 form a heterodimer, crucial for immune response. The drug suramin inhibits this interaction, potentially preventing complement-mediated hemolysis by altering protein oligomerization.
Area of Science:
- Biochemistry
- Immunology
- Molecular Biology
Background:
- The terminal complement pathway involves proteins C5, C8, and C9.
- Understanding protein-protein interactions is key to deciphering complement function and dysfunction.
Purpose of the Study:
- To investigate the association of terminal complement proteins C8 and C9.
- To elucidate the mechanism by which suramin affects complement protein interactions and inhibits hemolysis.
Main Methods:
- Analytical ultracentrifugation
- Multi-angle laser light scattering
- Fluorescence spectroscopy
Main Results:
- Native C8 and C9 form a temperature- and ionic strength-dependent heterodimer.
- Electrostatic forces significantly contribute to C8-C9 binding.
- Suramin induces C8 trimerization and C9 dimerization, inhibiting complement-mediated hemolysis.
- Suramin binds to specific sites on C8 and C9 oligomers, with evidence of nonionic interactions.
Conclusions:
- The interaction between C8 and C9 is primarily driven by electrostatic forces.
- Suramin's ability to inhibit complement-mediated hemolysis is linked to its induction of C8 and C9 oligomerization.
- Suramin exhibits complex binding behavior to complement proteins, involving both ionic and nonionic interactions.