BIROn - Birkbeck Institutional Research Online

    CryoEM reveals how the complement membrane attack complex ruptures lipid bilayers

    Menny, A. and Serna, M. and Boyd, C.M. and Gardner, S. and Joseph, A.P. and Morgan, B.P. and Topf, Maya and Brooks, N.J. and Bubeck, D. (2018) CryoEM reveals how the complement membrane attack complex ruptures lipid bilayers. Nature Communications 9 (1), ISSN 2041-1723.

    [img]
    Preview
    Text
    25544.pdf - Published Version of Record
    Available under License Creative Commons Attribution.

    Download (3MB) | Preview

    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.

    Metadata

    Item Type: Article
    School: Birkbeck Faculties and Schools > Faculty of Science > School of Natural Sciences
    Depositing User: Administrator
    Date Deposited: 17 Dec 2018 08:13
    Last Modified: 02 Aug 2023 17:47
    URI: https://eprints.bbk.ac.uk/id/eprint/25544

    Statistics

    Activity Overview
    6 month trend
    288Downloads
    6 month trend
    162Hits

    Additional statistics are available via IRStats2.

    Archive Staff Only (login required)

    Edit/View Item Edit/View Item