IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v5y2014i1d10.1038_ncomms6272.html
   My bibliography  Save this article

Kinetic modulation of a disordered protein domain by phosphorylation

Author

Listed:
  • Nathaniel Stanley

    (Computational Biophysics Laboratory (GRIB-IMIM), Universitat Pompeu Fabra, Barcelona Biomedical Research Park (PRBB))

  • Santiago Esteban-Martín

    (Joint BSC-IRB-CRG Research Programme in Computational Biology, Barcelona Supercomputing Center - BSC)

  • Gianni De Fabritiis

    (Computational Biophysics Laboratory (GRIB-IMIM), Universitat Pompeu Fabra, Barcelona Biomedical Research Park (PRBB)
    Institució Catalana de Recerca i Estudis Avançats)

Abstract

Phosphorylation is a major post-translational mechanism of regulation that frequently targets disordered protein domains, but it remains unclear how phosphorylation modulates disordered states of proteins. Here we determine the kinetics and energetics of a disordered protein domain the kinase-inducible domain (KID) of the transcription factor CREB and that of its phosphorylated form pKID, using high-throughput molecular dynamic simulations. We identify the presence of a metastable, partially ordered state with a 60-fold slowdown in conformational kinetics that arises due to phosphorylation, kinetically stabilizing residues known to participate in an early binding intermediate. We show that this effect is only partially reconstituted by mutation to glutamate, indicating that the phosphate is uniquely required for the long-lived state to arise. This mechanism of kinetic modulation could be important for regulation beyond conformational equilibrium shifts.

Suggested Citation

  • Nathaniel Stanley & Santiago Esteban-Martín & Gianni De Fabritiis, 2014. "Kinetic modulation of a disordered protein domain by phosphorylation," Nature Communications, Nature, vol. 5(1), pages 1-8, December.
    • Handle: RePEc:nat:natcom:v:5:y:2014:i:1:d:10.1038_ncomms6272
    DOI: 10.1038/ncomms6272
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/ncomms6272
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/ncomms6272?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
    ---><---

    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_ncomms6272. 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.