IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v7y2016i1d10.1038_ncomms10587.html
   My bibliography  Save this article

Structural basis of complement membrane attack complex formation

Author

Listed:
  • Marina Serna

    (Imperial College London, Sir Ernst Chain Building, South Kensington Campus, London SW7 2AZ, UK)

  • Joanna L. Giles

    (Institute of Infection and Immunity, School of Medicine, Cardiff University)

  • B. Paul Morgan

    (Institute of Infection and Immunity, School of Medicine, Cardiff University)

  • Doryen Bubeck

    (Imperial College London, Sir Ernst Chain Building, South Kensington Campus, London SW7 2AZ, UK)

Abstract

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.

Suggested Citation

  • Marina Serna & Joanna L. Giles & B. Paul Morgan & Doryen Bubeck, 2016. "Structural basis of complement membrane attack complex formation," Nature Communications, Nature, vol. 7(1), pages 1-7, April.
    • Handle: RePEc:nat:natcom:v:7:y:2016:i:1:d:10.1038_ncomms10587
    DOI: 10.1038/ncomms10587
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/ncomms10587
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/ncomms10587?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    Citations

    Citations are extracted by the CitEc Project, subscribe to its RSS feed for this item.
    as


    Cited by:

    1. Hunter L. Abrahamsen & Tristan C. Sanford & Casie E. Collamore & Bronte A. Johnstone & Michael J. Coyne & Leonor García-Bayona & Michelle P. Christie & Jordan C. Evans & Allison J. Farrand & Katia Flo, 2024. "Distant relatives of a eukaryotic cell-specific toxin family evolved a complement-like mechanism to kill bacteria," Nature Communications, Nature, vol. 15(1), pages 1-15, December.
    2. Emma C. Couves & Scott Gardner & Tomas B. Voisin & Jasmine K. Bickel & Phillip J. Stansfeld & Edward W. Tate & Doryen Bubeck, 2023. "Structural basis for membrane attack complex inhibition by CD59," Nature Communications, Nature, vol. 14(1), pages 1-13, December.
    3. Anaïs Menny & Marie V. Lukassen & Emma C. Couves & Vojtech Franc & Albert J. R. Heck & Doryen Bubeck, 2021. "Structural basis of soluble membrane attack complex packaging for clearance," Nature Communications, Nature, vol. 12(1), pages 1-11, December.
    4. Fang Jiao & François Dehez & Tao Ni & Xiulian Yu & Jeremy S. Dittman & Robert Gilbert & Christophe Chipot & Simon Scheuring, 2022. "Perforin-2 clockwise hand-over-hand pre-pore to pore transition mechanism," Nature Communications, Nature, vol. 13(1), pages 1-13, December.
    5. Sunita Gulati & Frank J Beurskens & Bart-Jan de Kreuk & Marcel Roza & Bo Zheng & Rosane B DeOliveira & Jutamas Shaughnessy & Nancy A Nowak & Ronald P Taylor & Marina Botto & Xianbao He & Robin R Ingal, 2019. "Complement alone drives efficacy of a chimeric antigonococcal monoclonal antibody," PLOS Biology, Public Library of Science, vol. 17(6), pages 1-29, June.

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:natcom:v:7:y:2016:i:1:d:10.1038_ncomms10587. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    We have no bibliographic references for this item. You can help adding them by using this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.