Complement cascade

A2ML1 is a human protease inhibitor belonging to the A2M protein family. In this study, the authors determine structures of A2ML1 before and after protease inhibition and investigate its mechanism of action.

Complement activation on foreign cell surfaces leads to the generation of complement opsonins, which activate complement receptor type 3 (CR3) and pathogen clearance by macrophages. Here, the authors reveal structural basis of the interaction between human opsonin iC3b and the von Willebrand A inserted domain of the α chain of CR3.

Ruiz-Molina et al. design a synthetic protein, MFHR13, as a multi-target complement regulator. They demonstrate that it protects sheep erythrocytes from complement attack exhibiting 26 and 4-fold the regulatory activity of eculizumab and human Factor H, respectively, which highlights its therapeutic potential.