IDEAS home Printed from https://ideas.repec.org/a/nat/nature/v474y2011i7353d10.1038_nature10099.html
   My bibliography  Save this article

Single-molecule fluorescence reveals sequence-specific misfolding in multidomain proteins

Author

Listed:
  • Madeleine B. Borgia

    (University of Cambridge Chemical Laboratory, Lensfield Road, Cambridge CB2 1EW, UK
    Biochemisches Institut, Universität Zürich, Winterthurerstrasse 190, 8057 Zürich, Switzerland)

  • Alessandro Borgia

    (Biochemisches Institut, Universität Zürich, Winterthurerstrasse 190, 8057 Zürich, Switzerland)

  • Robert B. Best

    (University of Cambridge Chemical Laboratory, Lensfield Road, Cambridge CB2 1EW, UK)

  • Annette Steward

    (University of Cambridge Chemical Laboratory, Lensfield Road, Cambridge CB2 1EW, UK)

  • Daniel Nettels

    (Biochemisches Institut, Universität Zürich, Winterthurerstrasse 190, 8057 Zürich, Switzerland)

  • Bengt Wunderlich

    (Biochemisches Institut, Universität Zürich, Winterthurerstrasse 190, 8057 Zürich, Switzerland)

  • Benjamin Schuler

    (Biochemisches Institut, Universität Zürich, Winterthurerstrasse 190, 8057 Zürich, Switzerland)

  • Jane Clarke

    (University of Cambridge Chemical Laboratory, Lensfield Road, Cambridge CB2 1EW, UK)

Abstract

When protein folding goes awry Three in four human proteins have multiple domains, and the tendency of these proteins to aggregate increases with amino-acid sequence similarity. Single-molecule biophysics experiments now show that the misfolding is caused by strand-swapping between adjacent domains, and that diversification of sequence between neighbouring domains lowers the probability of misfolding. The work also indicates that such misfolding events are under kinetic rather than thermodynamic control. Because domain-swapped protein species have been implicated in various misfolding diseases, prevention of inter-domain misfolding may be protective against aggregation disorders.

Suggested Citation

  • Madeleine B. Borgia & Alessandro Borgia & Robert B. Best & Annette Steward & Daniel Nettels & Bengt Wunderlich & Benjamin Schuler & Jane Clarke, 2011. "Single-molecule fluorescence reveals sequence-specific misfolding in multidomain proteins," Nature, Nature, vol. 474(7353), pages 662-665, June.
    • Handle: RePEc:nat:nature:v:474:y:2011:i:7353:d:10.1038_nature10099
    DOI: 10.1038/nature10099
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/nature10099
    File Function: Abstract
    Download Restriction: Access to the full text of the articles in this series is restricted.
    File URL: https://libkey.io/10.1038/nature10099?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
    ---><---

    As the access to this document is restricted, you may want to search for a different version of it.

    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:nature:v:474:y:2011:i:7353:d:10.1038_nature10099. 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.