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Structural basis for membrane attack complex inhibition by CD59

Author

Listed:
  • Emma C. Couves

    (Imperial College London)

  • Scott Gardner

    (Imperial College London)

  • Tomas B. Voisin

    (Imperial College London)

  • Jasmine K. Bickel

    (Imperial College London
    Imperial College London)

  • Phillip J. Stansfeld

    (The University of Warwick)

  • Edward W. Tate

    (Imperial College London)

  • Doryen Bubeck

    (Imperial College London)

Abstract

CD59 is an abundant immuno-regulatory receptor that protects human cells from damage during complement activation. Here we show how the receptor binds complement proteins C8 and C9 at the membrane to prevent insertion and polymerization of membrane attack complex (MAC) pores. We present cryo-electron microscopy structures of two inhibited MAC precursors known as C5b8 and C5b9. We discover that in both complexes, CD59 binds the pore-forming β-hairpins of C8 to form an intermolecular β-sheet that prevents membrane perforation. While bound to C8, CD59 deflects the cascading C9 β-hairpins, rerouting their trajectory into the membrane. Preventing insertion of C9 restricts structural transitions of subsequent monomers and indirectly halts MAC polymerization. We combine our structural data with cellular assays and molecular dynamics simulations to explain how the membrane environment impacts the dual roles of CD59 in controlling pore formation of MAC, and as a target of bacterial virulence factors which hijack CD59 to lyse human cells.

Suggested Citation

  • 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.
    • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-36441-z
    DOI: 10.1038/s41467-023-36441-z
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    References listed on IDEAS

    as
    1. Yining Jiang & Batiste Thienpont & Vinay Sapuru & Richard K. Hite & Jeremy S. Dittman & James N. Sturgis & Simon Scheuring, 2022. "Membrane-mediated protein interactions drive membrane protein organization," Nature Communications, Nature, vol. 13(1), pages 1-14, December.
    2. Kathryn Tunyasuvunakool & Jonas Adler & Zachary Wu & Tim Green & Michal Zielinski & Augustin Žídek & Alex Bridgland & Andrew Cowie & Clemens Meyer & Agata Laydon & Sameer Velankar & Gerard J. Kleywegt, 2021. "Highly accurate protein structure prediction for the human proteome," Nature, Nature, vol. 596(7873), pages 590-596, August.
    3. 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.
    4. John Jumper & Richard Evans & Alexander Pritzel & Tim Green & Michael Figurnov & Olaf Ronneberger & Kathryn Tunyasuvunakool & Russ Bates & Augustin Žídek & Anna Potapenko & Alex Bridgland & Clemens Me, 2021. "Highly accurate protein structure prediction with AlphaFold," Nature, Nature, vol. 596(7873), pages 583-589, August.
    5. Anaïs Menny & Marina Serna & Courtney M. Boyd & Scott Gardner & Agnel Praveen Joseph & B. Paul Morgan & Maya Topf & Nicholas J. Brooks & Doryen Bubeck, 2018. "CryoEM reveals how the complement membrane attack complex ruptures lipid bilayers," Nature Communications, Nature, vol. 9(1), pages 1-11, December.
    6. Nita R. Shah & Tomas B. Voisin & Edward S. Parsons & Courtney M. Boyd & Bart W. Hoogenboom & Doryen Bubeck, 2020. "Structural basis for tuning activity and membrane specificity of bacterial cytolysins," Nature Communications, Nature, vol. 11(1), pages 1-10, December.
    7. 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.
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