Complement cascade

It is generally thought that complement activation in human membranous nephropathy (MN) occurs predominantly via the lectin or alternative pathway. Here, the authors show that the classical pathway is the dominant form of complement activation in MN and a pathogenic driver of the disease.

The cryo-EM structure of monoclonal antibody aE11 bound to polyC9 reveals that the binding site within the Membrane Attack Complex is a quaternary discontinuous epitope formed by two separate surfaces of the oligomeric C9 periphery.

Therapeutic modulation of the complement system has gained interest over the past two decades. Here, the authors provide molecular-level insight into the mode-of-action, target selectivity and species specificity of the compstatin family of complement inhibitors, which entered the clinic in 2021.

Edwardsiella tarda TraT promotes cellular infection and serves as an anti-complement factor, shedding light on the mechanisms of E. tarda’s strong evasion of killing by the host.