Structure of human complement C8, a precursor to membrane attack.
Bottom Line: 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.
Affiliation: University of Oxford, Wellcome Trust Centre for Human Genetics, Oxford OX3 7BN, UK.Show MeSH
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Mentions: C8, isolated from plasma and purified under physiological conditions,10 is a stable, homogenous complex composed of three subunits, C8α, C8β, and C8γ, in which the intersubunit interactions remain intact (Fig. S1). Negatively stained C8 complexes were visualized by electron microscopy. Raw images (Fig. 1a) were aligned using reference-free alignment and classified into groups (Fig. 1b). Two-dimensional (2D) averages show that C8 has two distinct regions. The larger of the two appears globular and pseudo-2-fold symmetric with less density in the middle. The smaller one protrudes from this core.
Affiliation: University of Oxford, Wellcome Trust Centre for Human Genetics, Oxford OX3 7BN, UK.