@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}
}

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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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