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Nat Commun. 2018 Dec 14;9(1):5316. doi: 10.1038/s41467-018-07653-5.

CryoEM reveals how the complement membrane attack complex ruptures lipid bilayers.

Author information

Department of Life Sciences, Sir Ernst Chain Building, Imperial College London, London, SW7 2AZ, UK.
Spanish National Cancer Research Centre, CNIO, Melchor Fernández Almagro, 3.28029, Madrid, Spain.
Institute of Structural and Molecular Biology, Department of Biological Sciences, Birkbeck, University of London, Malet Street, London, WC1E 7HX, UK.
Scientific Computing Department, Science and Technology Facilities Council, Research Complex at Harwell, Didcot, OX11 0FA, UK.
Division of Infection and Immunity, School of Medicine, Cardiff University, Heath Park, Cardiff, CF14 4XN, UK.
Department of Chemistry, Imperial College London, London, SW7 2AZ, UK.
Department of Life Sciences, Sir Ernst Chain Building, Imperial College London, London, SW7 2AZ, UK.


The membrane attack complex (MAC) is one of the immune system's first responders. Complement proteins assemble on target membranes to form pores that lyse pathogens and impact tissue homeostasis of self-cells. How MAC disrupts the membrane barrier remains unclear. Here we use electron cryo-microscopy and flicker spectroscopy to show that MAC interacts with lipid bilayers in two distinct ways. Whereas C6 and C7 associate with the outer leaflet and reduce the energy for membrane bending, C8 and C9 traverse the bilayer increasing membrane rigidity. CryoEM reconstructions reveal plasticity of the MAC pore and demonstrate how C5b6 acts as a platform, directing assembly of a giant β-barrel whose structure is supported by a glycan scaffold. Our work provides a structural basis for understanding how β-pore forming proteins breach the membrane and reveals a mechanism for how MAC kills pathogens and regulates cell functions.

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