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CryoEM reveals how the complement membrane attack complex ruptures lipid bilayers

Menny, Anaïs, Serna, Marina, Boyd, Courtney M., Gardner, Scott, Joseph, Agnel Praveen, Morgan, B. Paul, Topf, Maya, Brooks, Nicholas J. and Bubeck, Doryen 2018. CryoEM reveals how the complement membrane attack complex ruptures lipid bilayers. Nature Communications 9 (1) , -. 10.1038/s41467-018-07653-5

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Abstract

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.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Medicine
Publisher: Nature Publishing Group
ISSN: 2041-1723
Date of First Compliant Deposit: 10 January 2019
Date of Acceptance: 12 November 2018
Last Modified: 14 Jan 2019 12:00
URI: http://orca.cf.ac.uk/id/eprint/118289

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