2026-05-17T01:41:13Zhttps://repisalud.isciii.es/rest/oai/requestoai:repisalud.isciii.es:20.500.12105/68622024-11-29T14:24:31Zcom_20.500.12105_2173com_20.500.12105_2051col_20.500.12105_19597
Repisalud
author
Menny, Anaïs
author
Serna, Marina
author
Boyd, Courtney M
author
Gardner, Scott
author
Joseph, Agnel Praveen
author
Morgan, B Paul
author
Topf, Maya
author
Brooks, Nicholas J
author
Bubeck, Doryen
funder
Wellcome Trust
2018-12-17T10:04:35Z
2018-12-17T10:04:35Z
2018-12-14
Nat Commun. 2018; 9(1): 5316.
10.1038/s41467-018-07653-5
2041-1723
2041-1723
Nature communications
30552328
http://hdl.handle.net/20.500.12105/6862
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.
eng
CryoEM reveals how the complement membrane attack complex ruptures lipid bilayers
journal article
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