In this section
@article{Serna:2016:10.1038/ncomms10587,
author = {Serna, Gil M and Bubeck, D and Giles, JL and Morgan, BP},
doi = {10.1038/ncomms10587},
journal = {Nature Communications},
pages = {1--7},
title = {Structural basis of complement membrane attack complex formation},
url = {http://dx.doi.org/10.1038/ncomms10587},
volume = {7},
year = {2016}
}
TY - JOUR
AB - In response to complement activation, the membrane attack complex (MAC) assembles from fluid-phase proteins to form pores in lipid bilayers. MAC directly lyses pathogens by a ‘multi-hit’ mechanism; however, sublytic MAC pores on host cells activate signalling pathways. Previous studies have described the structures of individual MAC components and subcomplexes; however, the molecular details of its assembly and mechanism of action remain unresolved. Here we report the electron cryo-microscopy structure of human MAC at subnanometre resolution. Structural analyses define the stoichiometry of the complete pore and identify a network of interaction interfaces that determine its assembly mechanism. MAC adopts a ‘split-washer’ configuration, in contrast to the predicted closed ring observed for perforin and cholesterol-dependent cytolysins. Assembly precursors partially penetrate the lipid bilayer, resulting in an irregular β-barrel pore. Our results demonstrate how differences in symmetric and asymmetric components of the MAC underpin a molecular basis for pore formation and suggest a mechanism of action that extends beyond membrane penetration.
AU - Serna,Gil M
AU - Bubeck,D
AU - Giles,JL
AU - Morgan,BP
DO - 10.1038/ncomms10587
EP - 7
PY - 2016///
SN - 2041-1723
SP - 1
TI - Structural basis of complement membrane attack complex formation
T2 - Nature Communications
UR - http://dx.doi.org/10.1038/ncomms10587
UR - https://www.nature.com/articles/ncomms10587
UR - http://hdl.handle.net/10044/1/29239
VL - 7
ER -
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