IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v7y2016i1d10.1038_ncomms12163.html
   My bibliography  Save this article

Mass spectrometry locates local and allosteric conformational changes that occur on cofactor binding

Author

Listed:
  • Rebecca Beveridge

    (Michael Barber Centre for Collaborative Mass Spectrometry, School of Chemistry, Centre for Synthetic Biology of Fine and Speciality Chemicals, Manchester Institute of Biotechnology, University of Manchester)

  • Lukasz G. Migas

    (Michael Barber Centre for Collaborative Mass Spectrometry, School of Chemistry, Centre for Synthetic Biology of Fine and Speciality Chemicals, Manchester Institute of Biotechnology, University of Manchester)

  • Karl A. P. Payne

    (Michael Barber Centre for Collaborative Mass Spectrometry, School of Chemistry, Centre for Synthetic Biology of Fine and Speciality Chemicals, Manchester Institute of Biotechnology, University of Manchester)

  • Nigel S. Scrutton

    (Michael Barber Centre for Collaborative Mass Spectrometry, School of Chemistry, Centre for Synthetic Biology of Fine and Speciality Chemicals, Manchester Institute of Biotechnology, University of Manchester)

  • David Leys

    (Michael Barber Centre for Collaborative Mass Spectrometry, School of Chemistry, Centre for Synthetic Biology of Fine and Speciality Chemicals, Manchester Institute of Biotechnology, University of Manchester)

  • Perdita E. Barran

    (Michael Barber Centre for Collaborative Mass Spectrometry, School of Chemistry, Centre for Synthetic Biology of Fine and Speciality Chemicals, Manchester Institute of Biotechnology, University of Manchester)

Abstract

Fdc1 is a decarboxylase enzyme that requires the novel prenylated FMN cofactor for activity. Here, we use it as an exemplar system to show how native top-down and bottom-up mass spectrometry can measure the structural effect of cofactor binding by a protein. For Fdc1Ubix, the cofactor confers structural stability to the enzyme. IM–MS shows the holo protein to exist in four closely related conformational families, the populations of which differ in the apo form; the two smaller families are more populated in the presence of the cofactor and depopulated in its absence. These findings, supported by MD simulations, indicate a more open structure for the apo form. HDX-MS reveals that while the dominant structural changes occur proximal to the cofactor-binding site, rearrangements on cofactor binding are evident throughout the protein, predominantly attributable to allosteric conformational tightening, consistent with IM–MS data.

Suggested Citation

  • Rebecca Beveridge & Lukasz G. Migas & Karl A. P. Payne & Nigel S. Scrutton & David Leys & Perdita E. Barran, 2016. "Mass spectrometry locates local and allosteric conformational changes that occur on cofactor binding," Nature Communications, Nature, vol. 7(1), pages 1-9, November.
    • Handle: RePEc:nat:natcom:v:7:y:2016:i:1:d:10.1038_ncomms12163
    DOI: 10.1038/ncomms12163
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/ncomms12163
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/ncomms12163?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:7:y:2016:i:1:d:10.1038_ncomms12163. 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.