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Electrostatic and steric effects underlie acetylation-induced changes in ubiquitin structure and function

Author

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  • Simon Maria Kienle

    (University of Konstanz
    University of Konstanz)

  • Tobias Schneider

    (University of Konstanz
    University of Konstanz)

  • Katrin Stuber

    (University of Konstanz
    University of Konstanz
    University of Konstanz)

  • Christoph Globisch

    (University of Konstanz)

  • Jasmin Jansen

    (University of Konstanz
    University of Konstanz)

  • Florian Stengel

    (University of Konstanz
    University of Konstanz)

  • Christine Peter

    (University of Konstanz
    University of Konstanz)

  • Andreas Marx

    (University of Konstanz
    University of Konstanz)

  • Michael Kovermann

    (University of Konstanz
    University of Konstanz)

  • Martin Scheffner

    (University of Konstanz
    University of Konstanz)

Abstract

Covalent attachment of ubiquitin (Ub) to proteins is a highly versatile posttranslational modification. Moreover, Ub is not only a modifier but itself is modified by phosphorylation and lysine acetylation. However, the functional consequences of Ub acetylation are poorly understood. By generation and comprehensive characterization of all seven possible mono-acetylated Ub variants, we show that each acetylation site has a particular impact on Ub structure. This is reflected in selective usage of the acetylated variants by different E3 ligases and overlapping but distinct interactomes, linking different acetylated variants to different cellular pathways. Notably, not only electrostatic but also steric effects contribute to acetylation-induced changes in Ub structure and, thus, function. Finally, we provide evidence that p300 acts as a position-specific Ub acetyltransferase and HDAC6 as a general Ub deacetylase. Our findings provide intimate insights into the structural and functional consequences of Ub acetylation and highlight the general importance of Ub acetylation.

Suggested Citation

  • 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.
  • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-33087-1
    DOI: 10.1038/s41467-022-33087-1
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    References listed on IDEAS

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