Schematic representation of the proposed mechanism of endothelial damage by the hyperfunctional C3-convertase, associated with the FB mutations D²⁵⁴G and K³²⁵N. The mutant FB binds to C3(H2O) and C3b with increased affinity. These C3-convertases are resistant to FH-assisted decay. The increased half-life and the loss of regulation of the fluid phase and surface C3-convertases led to increased C3 deposition on quiescent and damaged endothelium. Potentially mutant FB could bind to iC3b and form a C3-convertase on the inactivated C3 fragment. The formation of sC5b-9 and liberation of C5a could be associated with a procoagulant phenotype and aHUS.