FIGURE 6.
Schematic summarizing the observed interactions between FH and CRP. A, unbound FH exists as 5–15% dimer in equilibrium with monomeric FH with a monomer-dimer KD of 28 μm and with higher oligomers of FH formed by contacts between successive pairs of SCR-7 and SCR-20 domains. B, pentameric CRP binds to FH at either SCR-7 or SCR-20 with a reduced KD of 4.2 μm. The interaction blocks the formation of FH dimers and CRP decamers. Two molecules of CRP can bind simultaneously to one FH molecule. One molecule of CRP may be able to bind one molecule of FH at SCR-7 and SCR-20 at two different sites, in which case FH adopts a compact conformation. C, schematic illustration of how CRP can recruit FH (Tyr-402) onto damaged host cells at both SCR-7 (with a KD value of 4 μm) and SCR-20. This positions SCR-1/4 appropriately to regulate the degradation of surface-bound C3b, limiting complement activation at the host cell surface. In contrast, SCR-7 in FH (His-402) and SCR-20 interact less well with CRP, with similar KD values of 12 and 15 μm, respectively. The schematic arbitrarily shows SCR-20 bound to CRP, whereas SCR-7 is not bound; accordingly FH (His-402) is less able to regulate C3b degradation.