IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v5y2014i1d10.1038_ncomms6491.html
   My bibliography  Save this article

Calcium-induced conformational changes of the regulatory domain of human mitochondrial aspartate/glutamate carriers

Author

Listed:
  • Chancievan Thangaratnarajah

    (The Medical Research Council, Mitochondrial Biology Unit)

  • Jonathan J. Ruprecht

    (The Medical Research Council, Mitochondrial Biology Unit)

  • Edmund R. S. Kunji

    (The Medical Research Council, Mitochondrial Biology Unit)

Abstract

The transport activity of human mitochondrial aspartate/glutamate carriers is central to the malate–aspartate shuttle, urea cycle, gluconeogenesis and myelin synthesis. They have a unique three-domain structure, comprising a calcium-regulated N-terminal domain with eight EF-hands, a mitochondrial carrier domain, and a C-terminal domain. Here we present the calcium-bound and calcium-free structures of the N- and C-terminal domains, elucidating the mechanism of calcium regulation. Unexpectedly, EF-hands 4–8 are involved in dimerization of the carrier and form a static unit, whereas EF-hands 1–3 form a calcium-responsive mobile unit. On calcium binding, an amphipathic helix of the C-terminal domain binds to the N-terminal domain, opening a vestibule. In the absence of calcium, the mobile unit closes the vestibule. Opening and closing of the vestibule might regulate access of substrates to the carrier domain, which is involved in their transport. These structures provide a framework for understanding cases of the mitochondrial disease citrin deficiency.

Suggested Citation

  • Chancievan Thangaratnarajah & Jonathan J. Ruprecht & Edmund R. S. Kunji, 2014. "Calcium-induced conformational changes of the regulatory domain of human mitochondrial aspartate/glutamate carriers," Nature Communications, Nature, vol. 5(1), pages 1-12, December.
    • Handle: RePEc:nat:natcom:v:5:y:2014:i:1:d:10.1038_ncomms6491
    DOI: 10.1038/ncomms6491
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/ncomms6491
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/ncomms6491?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. Vasiliki Mavridou & Martin S. King & Sotiria Tavoulari & Jonathan J. Ruprecht & Shane M. Palmer & Edmund R. S. Kunji, 2022. "Substrate binding in the mitochondrial ADP/ATP carrier is a step-wise process guiding the structural changes in the transport cycle," Nature Communications, Nature, vol. 13(1), pages 1-12, December.
    2. Yuwan Chen & Wen Zhou & Yufei Xia & Weijie Zhang & Qun Zhao & Xinwei Li & Hang Gao & Zhen Liang & Guanghui Ma & Kaiguang Yang & Lihua Zhang & Yukui Zhang, 2023. "Targeted cross-linker delivery for the in situ mapping of protein conformations and interactions in mitochondria," Nature Communications, Nature, vol. 14(1), pages 1-16, 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:5:y:2014:i:1:d:10.1038_ncomms6491. 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.