Structure of human complement C8, a precursor to membrane attack

Journal article

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: Bubeck, D; Roversi, P; Donev, R; Morgan, B; Llorca, O

• Publication status: Published
• Peer review status: Peer reviewed
• Publisher: Elsevier
• Journal: Journal of Molecular Biology
• Volume: 405
• Issue: 2
• Pages: 325-330
• Publication date: 2011-01-01
• DOI: 10.1016/j.jmb.2010.10.031
• ISSN: 00222836
• Language: English
• Keywords: membrane attack complex (MAC); complement; terminal pathway; C8; 3D electron microscopy
• Subjects: Pathology; Biochemistry; Genetics (medical sciences)