title: Structure of human complement C8, a precursor to membrane attack.
abstract: Complement component C8 plays a pivotal role in the formation of the membrane attack complex (MAC), an important antibacterial immune effector. C8 initiates membrane penetration and coordinates MAC pore formation. High-resolution structures of C8 subunits have provided some insight into the function of the C8 heterotrimer; however, there is no structural information describing how the intersubunit organization facilitates MAC assembly. We have determined the structure of C8 by electron microscopy and fitted the C8α-MACPF (membrane attack complex/perforin)-C8γ co-crystal structure and a homology model for C8β-MACPF into the density. Here, we demonstrate that both the C8γ protrusion and the C8α-MACPF region that inserts into the membrane upon activation are accessible.
authors.affiliation: University of Oxford, Wellcome Trust Centre for Human Genetics, Oxford OX3 7BN, UK.
authors.forename: Doryen
authors.initials: D
authors.lastname: Bubeck
authors.forename: Pietro
authors.initials: P
authors.lastname: Roversi
authors.forename: Rossen
authors.initials: R
authors.lastname: Donev
authors.forename: B Paul
authors.initials: BP
authors.lastname: Morgan
authors.forename: Oscar
authors.initials: O
authors.lastname: Llorca
authors.forename: Susan M
authors.initials: SM
authors.lastname: Lea
mesh_terms: D002462:Cell Membrane / Q000378:metabolism*; D003185:Complement C8 / Q000737:chemistry* / Q000378:metabolism*; D015938:Complement Membrane Attack Complex / Q000737:chemistry* / Q000378:metabolism*; D006801:Humans; D007155:Immunologic Factors / Q000737:chemistry / Q000378:metabolism; D054353:Perforin / Q000737:chemistry / Q000378:metabolism*; D011485:Protein Binding; D017434:Protein Structure, Tertiary
chemical_list: D003185:Complement C8; D015938:Complement Membrane Attack Complex; D007155:Immunologic Factors; D054353:Perforin