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Structural and functional consequences of NEDD8 phosphorylation

Author

Listed:
  • Katrin Stuber

    (University of Konstanz
    University of Konstanz
    University of Konstanz)

  • Tobias Schneider

    (University of Konstanz
    University of Konstanz)

  • Jill Werner

    (University of Konstanz
    University of Konstanz)

  • Michael Kovermann

    (University of Konstanz
    University of Konstanz)

  • Andreas Marx

    (University of Konstanz
    University of Konstanz)

  • Martin Scheffner

    (University of Konstanz
    University of Konstanz)

Abstract

Ubiquitin (Ub) and Ub-like proteins (Ubls) such as NEDD8 are best known for their function as covalent modifiers of other proteins but they are also themselves subject to post-translational modifications including phosphorylation. While functions of phosphorylated Ub (pUb) have been characterized, the consequences of Ubl phosphorylation remain unclear. Here we report that NEDD8 can be phosphorylated at S65 - the same site as Ub - and that S65 phosphorylation affects the structural dynamics of NEDD8 and Ub in a similar manner. While both pUb and phosphorylated NEDD8 (pNEDD8) can allosterically activate the Ub ligase Parkin, they have different protein interactomes that in turn are distinct from those of unmodified Ub and NEDD8. Among the preferential pNEDD8 interactors are HSP70 family members and we show that pNEDD8 stimulates HSP70 ATPase activity more pronouncedly than unmodified NEDD8. Our findings highlight the general importance of Ub/NEDD8 phosphorylation and support the notion that the function of pUb/pNEDD8 does not require their covalent attachment to other proteins.

Suggested Citation

  • Katrin Stuber & Tobias Schneider & Jill Werner & Michael Kovermann & Andreas Marx & Martin Scheffner, 2021. "Structural and functional consequences of NEDD8 phosphorylation," Nature Communications, Nature, vol. 12(1), pages 1-15, December.
  • Handle: RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-26189-9
    DOI: 10.1038/s41467-021-26189-9
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    References listed on IDEAS

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    1. Simon Maria Kienle & Tobias Schneider & Katrin Stuber & Christoph Globisch & Jasmin Jansen & Florian Stengel & Christine Peter & Andreas Marx & Michael Kovermann & Martin Scheffner, 2022. "Electrostatic and steric effects underlie acetylation-induced changes in ubiquitin structure and function," Nature Communications, Nature, vol. 13(1), pages 1-16, December.

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