Structure of Human Complement C8, a Precursor to Membrane Attack

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 C8 alpha-MACPF (membrane attack complex/perforin)-C8 gamma co-crystal structure and a homology model for C8 beta-MACPF into the density. Here, we demonstrate that both the C8 gamma protrusion and the C8 alpha-MACPF region that inserts into the membrane upon activation are accessible. (C) 2010 Elsevier Ltd. All rights reserved.