Structure of human complement C8, a precursor to membrane attack.
Bottom Line: 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.Here, we demonstrate that both the C8γ protrusion and the C8α-MACPF region that inserts into the membrane upon activation are accessible.
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.