UCL Division of Biosciences


Factor H dimers by Sedimentation Equilibrium

Factor H dimers by Sedimentation Equilibrium
Complement Factor H is a 20-SCR plasma protein that is crucial for the regulation of complement activation in innate immunity by assisting the degradation of C3b.  The SCR-6/8 fragment of factor H contains a Tyr402His polymorphism that is a risk factor for age-related macular degeneration (AMD), a common cause of blindness in the elderly in the Western world.  Sedimentation equilibrium showed that the His402 allotype dimerised slightly more that the Tyr402 allotype.  This may be relevant to the sub-retinal protein deposits seen with AMD.
(a-c) and (d,e) The analyses for the His402 and Tyr402 allotypes of SCR-6/8 revealed a weak monomer-domer association between concentrations of 0.05 - 0.78 mg/ml from the apparent fitted molecular weights in single equilibrium fits.   
(f) The concentration dependence of the SCR-6/8 molecular weight supports a monomer-dimer equilibrium with a Kd of 40 µM. Extrapolation to zero concentration gave 23,200 ± 1,300 Da in good agreement with the sequence monomer molecular weight of 21,100 Da.

Publication: Fernando, A. N., Furtado, P. B., Clark, S. J., Gilbert, H. E., Day, A. J., Sim, R. B. & Perkins, S. J. (2007). Associative and structural properties of the region of complement Factor H encompassing the Tyr402His disease-related polymorphism and its interactions with heparin J Mol Biol. 368, 564-581.