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Structural basis of Notch O-glucosylation and O–xylosylation by mammalian protein–O-glucosyltransferase 1 (POGLUT1)

Author

Listed:
  • Zhijie Li

    (University of Toronto
    University of Toronto)

  • Michael Fischer

    (University of British Columbia)

  • Malathy Satkunarajah

    (University of Toronto
    University of Toronto)

  • Dongxia Zhou

    (University of Toronto
    University of Toronto)

  • Stephen G. Withers

    (University of British Columbia)

  • James M. Rini

    (University of Toronto
    University of Toronto)

Abstract

Protein O-glucosyltransferase 1/Rumi-mediated glucosylation of Notch epidermal growth factor-like (EGF-like) domains plays an important role in Notch signaling. Protein O-glucosyltransferase 1 shows specificity for folded EGF-like domains, it can only glycosylate serine residues in the C1XSXPC2 motif, and it possesses an uncommon dual donor substrate specificity. Using several EGF-like domains and donor substrate analogs, we have determined the structures of human Protein O-glucosyltransferase 1 substrate/product complexes that provide mechanistic insight into the basis for these properties. Notably, we show that Protein O-glucosyltransferase 1’s requirement for folded EGF-like domains also leads to its serine specificity and that two distinct local conformational states are likely responsible for its ability to transfer both glucose and xylose. We also show that Protein O-glucosyltransferase 1 possesses the potential to xylosylate a much broader range of EGF-like domain substrates than was previously thought. Finally, we show that Protein O-glucosyltransferase 1 has co-evolved with EGF-like domains of the type found in Notch.

Suggested Citation

  • Zhijie Li & Michael Fischer & Malathy Satkunarajah & Dongxia Zhou & Stephen G. Withers & James M. Rini, 2017. "Structural basis of Notch O-glucosylation and O–xylosylation by mammalian protein–O-glucosyltransferase 1 (POGLUT1)," Nature Communications, Nature, vol. 8(1), pages 1-12, December.
    • Handle: RePEc:nat:natcom:v:8:y:2017:i:1:d:10.1038_s41467-017-00255-7
    DOI: 10.1038/s41467-017-00255-7
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    Cited by:

    1. Francisco Leisico & Juneina Omeiri & Christine Narvor & Joël Beaudouin & Michael Hons & Daphna Fenel & Guy Schoehn & Yohann Couté & David Bonnaffé & Rabia Sadir & Hugues Lortat-Jacob & Rebekka Wild, 2022. "Structure of the human heparan sulfate polymerase complex EXT1-EXT2," Nature Communications, Nature, vol. 13(1), pages 1-11, December.

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