CFHR dimers bind C3b, acting as competitive antagonists of Factor H (CFH) binding (de Jorge et al. 2013, Tortajada et al. 2013). CFHR1, CFHR2, and CFHR5 have a dimerization motif within their amino-terminal domains that enables formation of three homodimers (CFHR1:CFHR1, CFHR2:CFHR2, CFHR5:CFHR5) and three heterodimers (CFHR1:CFHR2, CFHR1:CFHR5, and CFHR2:CFHR5). Multiple binding interactions and avidity enable these dimers to out-compete CFH at physiologically relevant concentrations. CFHR2 homodimers bind C3b while allowing C3 convertase formation, but the CFHR2 bound convertases does not cleave C3 (Eberhardt et al. 2013).

CFHR3 and CFHR4 do not contain the dimerization motif seen in CFHR1, 2 and 5 but compete with factor H for binding to C3b (Hellwage et al. 1999, Fritsche et al. 2010). CFHR4 exists predominantly as a dimer in plasma (Hellwage et al. 1999).

As the main function of CFH is down-regulation of C3 activation through the alternative pathway amplification loop, CFHR dimers interfere with the C3b inhibitory actions of CFH, a process termed deregulation (de Jorge et al. 2013, Tortajada et al. 2013).