Interactions between human complement components factor H, factor I and C3b.
Using a microtitre plate assay, direct binding between complement factors I and H was demonstrated, and ligand blotting indicated that factor H interacts with the heavy chain of factor I. Similarly, direct C3(NH3)-factor I and C3(NH3)-factor H binding was characterized [where C3(NH3) is a form of C3 that is cleaved by factor I in the presence of factor H]. Both factor H and factor I interacted with both chains of C3(NH3) in ligand blotting. Binding reactions between all three pairs of components were highly dependent on ionic strength, and showed similar pH optima. Binding assays with all three components present led to the following conclusions. (a) Binding sites for C3(NH3) and factor I on factor H do not overlap, and binding of factor I and C3(NH3) to soluble factor H promotes the weak factor I-C3(NH3) interaction. (b) Anomalies arise with immobilized factor H, which may be artefactual or may reflect the physiological situation. (c) Similarly, binding sites on factor I for C3(NH3) and for factor H do not overlap, and binding of factor H and C3(NH3) to factor I promotes direct factor H-C3(NH3) interactions. Based on these results, a model of the interactions between factor H, factor I and C3(NH3) leading to the processing of C3(NH3) is proposed.
Soames
C J
CJ
MRC Immunochemistry Unit, Department of Biochemistry, University of Oxford, U.K.
Sim
R B
RB
D002413:Cations, Divalent; D003179:Complement C3b / Q000378:metabolism*; D017242:Complement Factor H / Q000378:metabolism*; D003432:Cross-Linking Reagents; D005340:Fibrinogen / Q000378:metabolism*; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007457:Iodine Radioisotopes; D008024:Ligands; D008274:Magnesium / Q000378:metabolism; D009994:Osmolar Concentration; D011485:Protein Binding / Q000276:immunology; D015032:Zinc / Q000378:metabolism
C493495:CFH protein, human; D002413:Cations, Divalent; D003432:Cross-Linking Reagents; D007457:Iodine Radioisotopes; D008024:Ligands; D003179:Complement C3b; D017242:Complement Factor H; D005340:Fibrinogen; D008274:Magnesium; D015032:Zinc