IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v9y2018i1d10.1038_s41467-018-05717-0.html
   My bibliography  Save this article

The first transmembrane region of complement component-9 acts as a brake on its self-assembly

Author

Listed:
  • Bradley A. Spicer

    (23 Innovation Walk, Monash University
    23 Innovation Walk, Monash University)

  • Ruby H. P. Law

    (23 Innovation Walk, Monash University
    23 Innovation Walk, Monash University)

  • Tom T. Caradoc-Davies

    (23 Innovation Walk, Monash University
    Australian Synchrotron)

  • Sue M. Ekkel

    (23 Innovation Walk, Monash University
    23 Innovation Walk, Monash University)

  • Charles Bayly-Jones

    (23 Innovation Walk, Monash University
    23 Innovation Walk, Monash University)

  • Siew-Siew Pang

    (23 Innovation Walk, Monash University
    23 Innovation Walk, Monash University)

  • Paul J. Conroy

    (23 Innovation Walk, Monash University
    23 Innovation Walk, Monash University)

  • Georg Ramm

    (23 Innovation Walk, Monash University
    23 Innovation Walk, Monash University)

  • Mazdak Radjainia

    (Achtseweg Noord 5, Building)

  • Hariprasad Venugopal

    (23 Innovation Walk, Monash University
    23 Innovation Walk, Monash University)

  • James C. Whisstock

    (23 Innovation Walk, Monash University
    23 Innovation Walk, Monash University
    EMBL Australia, Monash University
    South East University-Monash Joint Institute, Institute of Life Sciences, Southeast University)

  • Michelle A. Dunstone

    (23 Innovation Walk, Monash University
    23 Innovation Walk, Monash University)

Abstract

Complement component 9 (C9) functions as the pore-forming component of the Membrane Attack Complex (MAC). During MAC assembly, multiple copies of C9 are sequentially recruited to membrane associated C5b8 to form a pore. Here we determined the 2.2 Å crystal structure of monomeric murine C9 and the 3.9 Å resolution cryo EM structure of C9 in a polymeric assembly. Comparison with other MAC proteins reveals that the first transmembrane region (TMH1) in monomeric C9 is uniquely positioned and functions to inhibit its self-assembly in the absence of C5b8. We further show that following C9 recruitment to C5b8, a conformational change in TMH1 permits unidirectional and sequential binding of additional C9 monomers to the growing MAC. This mechanism of pore formation contrasts with related proteins, such as perforin and the cholesterol dependent cytolysins, where it is believed that pre-pore assembly occurs prior to the simultaneous release of the transmembrane regions.

Suggested Citation

  • Bradley A. Spicer & Ruby H. P. Law & Tom T. Caradoc-Davies & Sue M. Ekkel & Charles Bayly-Jones & Siew-Siew Pang & Paul J. Conroy & Georg Ramm & Mazdak Radjainia & Hariprasad Venugopal & James C. Whis, 2018. "The first transmembrane region of complement component-9 acts as a brake on its self-assembly," Nature Communications, Nature, vol. 9(1), pages 1-7, December.
    • Handle: RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-018-05717-0
    DOI: 10.1038/s41467-018-05717-0
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-018-05717-0
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-018-05717-0?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. 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.

    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:9:y:2018:i:1:d:10.1038_s41467-018-05717-0. 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.