The membrane attack complex (MAC) of the complement terminal pathway is an important innate immune effector that lyses pathogens by forming cytotoxic pores in lipid bilayers. Genetic deficiencies found in MAC components lead to recurrent infections, while unregulated MAC formation causes host tissue damage. Therefore, understanding how MACs are assembled and regulated is of direct importance to human health.
Structural studies of soluble complexes have provided some insight into how complement proteins come together to form the MAC. However, structural information regarding the transmembrane pore is still lacking. Here we present the first three-dimensional structure of the MAC pore by cryo-electron microscopy. This data are crucial for defining a molecular mechanism underpinning the host immune response, and have broader implications for how bacterial toxins, that share a related structural motif, form pores.