IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v10y2019i1d10.1038_s41467-019-10167-3.html
   My bibliography  Save this article

The structural basis of translational control by eIF2 phosphorylation

Author

Listed:
  • Tomas Adomavicius

    (The University of Manchester)

  • Margherita Guaita

    (The University of Manchester)

  • Yu Zhou

    (The University of Manchester
    Old Road Campus Research Building Roosevelt Drive)

  • Martin D. Jennings

    (The University of Manchester)

  • Zakia Latif

    (The University of Manchester
    University of the Punjab)

  • Alan M. Roseman

    (The University of Manchester)

  • Graham D. Pavitt

    (The University of Manchester)

Abstract

Protein synthesis in eukaryotes is controlled by signals and stresses via a common pathway, called the integrated stress response (ISR). Phosphorylation of the translation initiation factor eIF2 alpha at a conserved serine residue mediates translational control at the ISR core. To provide insight into the mechanism of translational control we have determined the structures of eIF2 both in phosphorylated and unphosphorylated forms bound with its nucleotide exchange factor eIF2B by electron cryomicroscopy. The structures reveal that eIF2 undergoes large rearrangements to promote binding of eIF2α to the regulatory core of eIF2B comprised of the eIF2B alpha, beta and delta subunits. Only minor differences are observed between eIF2 and eIF2αP binding to eIF2B, suggesting that the higher affinity of eIF2αP for eIF2B drives translational control. We present a model for controlled nucleotide exchange and initiator tRNA binding to the eIF2/eIF2B complex.

Suggested Citation

  • Tomas Adomavicius & Margherita Guaita & Yu Zhou & Martin D. Jennings & Zakia Latif & Alan M. Roseman & Graham D. Pavitt, 2019. "The structural basis of translational control by eIF2 phosphorylation," Nature Communications, Nature, vol. 10(1), pages 1-10, December.
    • Handle: RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-019-10167-3
    DOI: 10.1038/s41467-019-10167-3
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-019-10167-3
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-019-10167-3?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. Michael Schoof & Lan Wang & J. Zachery Cogan & Rosalie E. Lawrence & Morgane Boone & Jennifer Deborah Wuerth & Adam Frost & Peter Walter, 2021. "Viral evasion of the integrated stress response through antagonism of eIF2-P binding to eIF2B," Nature Communications, Nature, vol. 12(1), pages 1-12, December.
    2. Katherine Labbé & Lauren LeBon & Bryan King & Ngoc Vu & Emily H. Stoops & Nina Ly & Austin E. Y. T. Lefebvre & Phillip Seitzer & Swathi Krishnan & Jin-Mi Heo & Bryson Bennett & Carmela Sidrauski, 2024. "Specific activation of the integrated stress response uncovers regulation of central carbon metabolism and lipid droplet biogenesis," Nature Communications, Nature, vol. 15(1), pages 1-21, 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:10:y:2019:i:1:d:10.1038_s41467-019-10167-3. 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.