IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v9y2018i1d10.1038_s41467-018-05725-0.html
   My bibliography  Save this article

A proline switch explains kinetic heterogeneity in a coupled folding and binding reaction

Author

Listed:
  • Franziska Zosel

    (University of Zurich
    Novo Nordisk A/S)

  • Davide Mercadante

    (University of Zurich)

  • Daniel Nettels

    (University of Zurich)

  • Benjamin Schuler

    (University of Zurich
    University of Zurich)

Abstract

The interactions of intrinsically disordered proteins (IDPs) with their molecular targets are essential for the regulation of many cellular processes. IDPs can perform their functions while disordered, and they may fold to structured conformations on binding. Here we show that the cis/trans isomerization of peptidyl−prolyl bonds can have a pronounced effect on the interactions of IDPs. By single-molecule spectroscopy, we identify a conserved proline residue in NCBD (the nuclear-coactivator binding domain of CBP) whose cis/trans isomerization in the unbound state modulates the association and dissociation rates with its binding partner, ACTR. As a result, NCBD switches on a time scale of tens of seconds between two populations that differ in their affinities to ACTR by about an order of magnitude. Molecular dynamics simulations indicate as a cause reduced packing of the complex for the cis isomer. Peptidyl-prolyl cis/trans isomerization may be an important previously unidentified mechanism for regulating IDP interactions.

Suggested Citation

  • Franziska Zosel & Davide Mercadante & Daniel Nettels & Benjamin Schuler, 2018. "A proline switch explains kinetic heterogeneity in a coupled folding and binding reaction," Nature Communications, Nature, vol. 9(1), pages 1-10, December.
    • Handle: RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-018-05725-0
    DOI: 10.1038/s41467-018-05725-0
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-018-05725-0
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-018-05725-0?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. Markus Götz & Anders Barth & Søren S. -R. Bohr & Richard Börner & Jixin Chen & Thorben Cordes & Dorothy A. Erie & Christian Gebhardt & Mélodie C. A. S. Hadzic & George L. Hamilton & Nikos S. Hatzakis , 2024. "Reply to: On the statistical foundation of a recent single molecule FRET benchmark," Nature Communications, Nature, vol. 15(1), pages 1-4, December.
    2. Frederik Friis Theisen & Andreas Prestel & Steffie Elkjær & Yannick H. A. Leurs & Nicholas Morffy & Lucia C. Strader & Charlotte O’Shea & Kaare Teilum & Birthe B. Kragelund & Karen Skriver, 2024. "Molecular switching in transcription through splicing and proline-isomerization regulates stress responses in plants," Nature Communications, Nature, vol. 15(1), pages 1-13, 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_s41467-018-05725-0. 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.