IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v8y2017i1d10.1038_ncomms14635.html
   My bibliography  Save this article

Allosteric modulation of peroxisomal membrane protein recognition by farnesylation of the peroxisomal import receptor PEX19

Author

Listed:
  • Leonidas Emmanouilidis

    (Institute of Structural Biology, Helmholtz Zentrum München
    Munich Center for Integrated Protein Science at Chair of Biomolecular NMR, Technische Universität München)

  • Ulrike Schütz

    (Institute of Structural Biology, Helmholtz Zentrum München
    Munich Center for Integrated Protein Science at Chair of Biomolecular NMR, Technische Universität München)

  • Konstantinos Tripsianes

    (CEITEC—Central European Institute of Technology, Masaryk University)

  • Tobias Madl

    (Institute of Structural Biology, Helmholtz Zentrum München
    Munich Center for Integrated Protein Science at Chair of Biomolecular NMR, Technische Universität München
    Institute of Molecular Biology and Biochemisty, Medical University of Graz)

  • Juliane Radke

    (Institute of Biochemistry and Pathobiochemistry, Faculty of Medicine, Ruhr University Bochum)

  • Robert Rucktäschel

    (Institute of Biochemistry and Pathobiochemistry, Faculty of Medicine, Ruhr University Bochum)

  • Matthias Wilmanns

    (EMBL Hamburg)

  • Wolfgang Schliebs

    (Institute of Biochemistry and Pathobiochemistry, Faculty of Medicine, Ruhr University Bochum)

  • Ralf Erdmann

    (Institute of Biochemistry and Pathobiochemistry, Faculty of Medicine, Ruhr University Bochum)

  • Michael Sattler

    (Institute of Structural Biology, Helmholtz Zentrum München
    Munich Center for Integrated Protein Science at Chair of Biomolecular NMR, Technische Universität München)

Abstract

The transport of peroxisomal membrane proteins (PMPs) requires the soluble PEX19 protein as chaperone and import receptor. Recognition of cargo PMPs by the C-terminal domain (CTD) of PEX19 is required for peroxisome biogenesis in vivo. Farnesylation at a C-terminal CaaX motif in PEX19 enhances the PMP interaction, but the underlying molecular mechanisms are unknown. Here, we report the NMR-derived structure of the farnesylated human PEX19 CTD, which reveals that the farnesyl moiety is buried in an internal hydrophobic cavity. This induces substantial conformational changes that allosterically reshape the PEX19 surface to form two hydrophobic pockets for the recognition of conserved aromatic/aliphatic side chains in PMPs. Mutations of PEX19 residues that either mediate farnesyl contacts or are directly involved in PMP recognition abolish cargo binding and cannot complement a ΔPEX19 phenotype in human Zellweger patient fibroblasts. Our results demonstrate an allosteric mechanism for the modulation of protein function by farnesylation.

Suggested Citation

  • Leonidas Emmanouilidis & Ulrike Schütz & Konstantinos Tripsianes & Tobias Madl & Juliane Radke & Robert Rucktäschel & Matthias Wilmanns & Wolfgang Schliebs & Ralf Erdmann & Michael Sattler, 2017. "Allosteric modulation of peroxisomal membrane protein recognition by farnesylation of the peroxisomal import receptor PEX19," Nature Communications, Nature, vol. 8(1), pages 1-13, April.
    • Handle: RePEc:nat:natcom:v:8:y:2017:i:1:d:10.1038_ncomms14635
    DOI: 10.1038/ncomms14635
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/ncomms14635
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/ncomms14635?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. Dzmitry Ashkinadze & Harindranath Kadavath & Aditya Pokharna & Celestine N. Chi & Michael Friedmann & Dean Strotz & Pratibha Kumari & Martina Minges & Riccardo Cadalbert & Stefan Königl & Peter Günter, 2022. "Atomic resolution protein allostery from the multi-state structure of a PDZ domain," Nature Communications, Nature, vol. 13(1), pages 1-10, 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:8:y:2017:i:1:d:10.1038_ncomms14635. 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.