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Oligomeric domain structure of human complement factor H by X-ray and neutron solution scattering
S J Perkins1, A S Nealis, R B Sim
1Department of Biochemistry and Chemistry, Royal Free Hospital School of Medicine, London, U.K.
Biochemistry
|March 19, 1991
Summary
Factor H, a complement system regulator, is dimeric with a V-shaped structure. Its short consensus repeats (SCRs) form extended conformations, influencing its solution structure and function.
Area of Science:
- Biochemistry
- Structural Biology
- Immunology
Background:
- Factor H is a critical regulatory protein of the complement system.
- It comprises 20 short consensus repeats (SCRs) or complement control protein (CCP) domains.
Purpose of the Study:
- To determine the solution structure of Factor H using biophysical methods.
- To investigate the structural impact of Zn2+ ions on Factor H.
Main Methods:
- High-flux synchrotron X-ray and neutron scattering.
- Analysis of scattering data using hydrodynamic models.
- Investigation of Factor H oligomerization in the presence of Zn2+.
Main Results:
- Factor H exists as a dimer with a molecular weight of 250,000–320,000.
- The dimeric structure is stable across a physiological pH range and concentrations.
- Zn2+ ions induce oligomerization of Factor H into structures of 4–10 monomers.
- Scattering data support a V-shaped model for Factor H, with two extended rods joined at a 5-degree angle.
- Individual SCR/CCP domains are spaced approximately 4 nm apart in a highly extended conformation.
Conclusions:
- The solution structure of Factor H is dimeric and highly extended.
- The V-shaped arrangement of SCR/CCP domains likely contributes to its regulatory function.
- Zn2+ binding alters Factor H's quaternary structure, potentially modulating its cofactor activity.