IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v7y2016i1d10.1038_ncomms10175.html
   My bibliography  Save this article

Structure of the polyisoprenyl-phosphate glycosyltransferase GtrB and insights into the mechanism of catalysis

Author

Listed:
  • Chiara Ardiccioni

    (Columbia University)

  • Oliver B. Clarke

    (Columbia University)

  • David Tomasek

    (Columbia University)

  • Habon A. Issa

    (George Washington University
    George Washington University)

  • Desiree C. von Alpen

    (George Washington University
    George Washington University)

  • Heather L. Pond

    (George Washington University
    George Washington University)

  • Surajit Banerjee

    (Cornell University, Argonne National Laboratory)

  • Kanagalaghatta R. Rajashankar

    (Cornell University, Argonne National Laboratory)

  • Qun Liu

    (New York Structural Biology Center, X4 Beamlines, Brookhaven National Laboratory)

  • Ziqiang Guan

    (Duke University Medical Center)

  • Chijun Li

    (Duke University Medical Center)

  • Brian Kloss

    (New York Consortium on Membrane Protein Structure, New York Structural Biology Center)

  • Renato Bruni

    (New York Consortium on Membrane Protein Structure, New York Structural Biology Center)

  • Edda Kloppmann

    (Bioinformatics and Computational Biology
    Institute for Advanced Study (TUM-IAS), TUM (Technische Universität München))

  • Burkhard Rost

    (Bioinformatics and Computational Biology
    Institute for Advanced Study (TUM-IAS), TUM (Technische Universität München))

  • M. Chiara Manzini

    (George Washington University
    George Washington University)

  • Lawrence Shapiro

    (Columbia University)

  • Filippo Mancia

    (Columbia University)

Abstract

The attachment of a sugar to a hydrophobic polyisoprenyl carrier is the first step for all extracellular glycosylation processes. The enzymes that perform these reactions, polyisoprenyl-glycosyltransferases (PI-GTs) include dolichol phosphate mannose synthase (DPMS), which generates the mannose donor for glycosylation in the endoplasmic reticulum. Here we report the 3.0Å resolution crystal structure of GtrB, a glucose-specific PI-GT from Synechocystis, showing a tetramer in which each protomer contributes two helices to a membrane-spanning bundle. The active site is 15 Å from the membrane, raising the question of how water-soluble and membrane-embedded substrates are brought into apposition for catalysis. A conserved juxtamembrane domain harbours disease mutations, which compromised activity in GtrB in vitro and in human DPM1 tested in zebrafish. We hypothesize a role of this domain in shielding the polyisoprenyl-phosphate for transport to the active site. Our results reveal the basis of PI-GT function, and provide a potential molecular explanation for DPM1-related disease.

Suggested Citation

  • Chiara Ardiccioni & Oliver B. Clarke & David Tomasek & Habon A. Issa & Desiree C. von Alpen & Heather L. Pond & Surajit Banerjee & Kanagalaghatta R. Rajashankar & Qun Liu & Ziqiang Guan & Chijun Li & , 2016. "Structure of the polyisoprenyl-phosphate glycosyltransferase GtrB and insights into the mechanism of catalysis," Nature Communications, Nature, vol. 7(1), pages 1-9, April.
    • Handle: RePEc:nat:natcom:v:7:y:2016:i:1:d:10.1038_ncomms10175
    DOI: 10.1038/ncomms10175
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/ncomms10175
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/ncomms10175?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_ncomms10175. 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.