Figure 4.

hC3Nb1 inhibits convertase assembly and FH-mediated FI cleavage of C3b caused by spatial overlap with FH and FB. A, superposition of the C3b–hC3Nb1 and the C3bB (PDB entry 2XWB) structures shows that the N122 linked glycan of FB overlaps significantly with the Nb. B–E, SEC analysis of the AP proconvertase with and without hC3Nb1. The Nb inhibits the formation of the AP proconvertase only when the Asn¹²²–linked glycan is present on FB. F, superposition of the C3b–hC3Nb1 structure onto the structure of C3b bound to FH CCP1–4 (PDB entry 2WII) reveals that the binding sites of FH CCP1 and the Nb overlap substantially. G, SDS-PAGE analysis of a FH-assisted FI cleavage assay showing that hC3Nb1 completely inhibits iC3b formation.