TY - JOUR AB - In response to complement activation, the membrane attack complex (MAC) assembles from fluid-phase proteins to form pores in lipid bilayers. MAC directly lyses pathogens by a ‘multi-hit’ mechanism; however, sublytic MAC pores on host cells activate signalling pathways. Previous studies have described the structures of individual MAC components and subcomplexes; however, the molecular details of its assembly and mechanism of action remain unresolved. Here we report the electron cryo-microscopy structure of human MAC at subnanometre resolution. Structural analyses define the stoichiometry of the complete pore and identify a network of interaction interfaces that determine its assembly mechanism. MAC adopts a ‘split-washer’ configuration, in contrast to the predicted closed ring observed for perforin and cholesterol-dependent cytolysins. Assembly precursors partially penetrate the lipid bilayer, resulting in an irregular β-barrel pore. Our results demonstrate how differences in symmetric and asymmetric components of the MAC underpin a molecular basis for pore formation and suggest a mechanism of action that extends beyond membrane penetration. AU - Serna,Gil M AU - Bubeck,D AU - Giles,JL AU - Morgan,BP DO - 10.1038/ncomms10587 EP - 7 PY - 2016/// SN - 2041-1723 SP - 1 TI - Structural basis of complement membrane attack complex formation T2 - Nature Communications UR - http://dx.doi.org/10.1038/ncomms10587 UR - https://www.nature.com/articles/ncomms10587 UR - http://hdl.handle.net/10044/1/29239 VL - 7 ER -