Structure of C8 -MACPF Reveals Mechanism of Membrane Attack in Complement Immune Defense

M. A. Hadders, D. X. Beringer, P. Gros
2007 Science  
Membrane attack is important for mammalian immune defense against invading microorganisms and infected host cells. Proteins of the complement membrane attack complex (MAC) and the protein perforin share a common MACPF domain that is responsible for membrane insertion and pore formation. We determined the crystal structure of the MACPF domain of complement component C8a at 2.5 angstrom resolution and show that it is structurally homologous to the bacterial, pore-forming, cholesterol-dependent
more » ... sterol-dependent cytolysins. The structure displays two regions that (in the bacterial cytolysins) refold into transmembrane b hairpins, forming the lining of a barrel pore. Local hydrophobicity explains why C8a is the first complement protein to insert into the membrane. The size of the MACPF domain is consistent with known C9 pore sizes. These data imply that these mammalian and bacterial cytolytic proteins share a common mechanism of membrane insertion.
doi:10.1126/science.1147103 pmid:17872444 fatcat:by3ahnvqcre4phepbxtkzh4v7a