The modular serine proteases of the complement cascade

► Domain rearrangements of ∼100 Å underlie regulation of complement protease cascade. ► Allosteric auto-activation of C1/MBL-associated modular proteases upon microbe binding. ► Structures of factor B, D, CVFB, C3bB and C3bBD reveal C3 convertase formation. ► Substrate-product (C3-C3b) binding drives C3 convertase in complement amplification. ► Regulators bind C3b to decay and degrade convertases to protect hosts.