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Ubiquitin and a charged loop regulate the ubiquitin E3 ligase activity of Ark2C

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  • Andrej Paluda

    (University of Otago
    TMDU Advanced Research Institute, Tokyo Medical and Dental University)

  • Adam J. Middleton

    (University of Otago)

  • Claudia Rossig

    (University of Otago)

  • Peter D. Mace

    (University of Otago)

  • Catherine L. Day

    (University of Otago)

Abstract

A large family of E3 ligases that contain both substrate recruitment and RING domains confer specificity within the ubiquitylation cascade. Regulation of RING E3s depends on modulating their ability to stabilise the RING bound E2~ubiquitin conjugate in the activated (or closed) conformation. Here we report the structure of the Ark2C RING bound to both a regulatory ubiquitin molecule and an activated E2~ubiquitin conjugate. The structure shows that the RING domain and non-covalently bound ubiquitin molecule together make contacts that stabilise the activated conformation of the conjugate, revealing why ubiquitin is a key regulator of Ark2C activity. We also identify a charged loop N-terminal to the RING domain that enhances activity by interacting with both the regulatory ubiquitin and ubiquitin conjugated to the E2. In addition, the structure suggests how Lys48-linked ubiquitin chains might be assembled by Ark2C and UbcH5b. Together this study identifies features common to RING E3s, as well elements that are unique to Ark2C and related E3s, which enhance assembly of ubiquitin chains.

Suggested Citation

  • Andrej Paluda & Adam J. Middleton & Claudia Rossig & Peter D. Mace & Catherine L. Day, 2022. "Ubiquitin and a charged loop regulate the ubiquitin E3 ligase activity of Ark2C," Nature Communications, Nature, vol. 13(1), pages 1-12, December.
    • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-28782-y
    DOI: 10.1038/s41467-022-28782-y
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    1. Christiane Niederländer & James J. Walsh & Vasso Episkopou & C. Michael Jones, 2001. "Arkadia enhances nodal-related signalling to induce mesendoderm," Nature, Nature, vol. 410(6830), pages 830-834, April.
    2. Leo Kiss & Dean Clift & Nadine Renner & David Neuhaus & Leo C. James, 2021. "RING domains act as both substrate and enzyme in a catalytic arrangement to drive self-anchored ubiquitination," Nature Communications, Nature, vol. 12(1), pages 1-12, December.
    3. Anna Plechanovová & Ellis G. Jaffray & Michael H. Tatham & James H. Naismith & Ronald T. Hay, 2012. "Structure of a RING E3 ligase and ubiquitin-loaded E2 primed for catalysis," Nature, Nature, vol. 489(7414), pages 115-120, September.
    4. Annie M. Sriramachandran & Katrin Meyer-Teschendorf & Stefan Pabst & Helle D. Ulrich & Niels H. Gehring & Kay Hofmann & Gerrit J. K. Praefcke & R. Jürgen Dohmen, 2019. "Arkadia/RNF111 is a SUMO-targeted ubiquitin ligase with preference for substrates marked with SUMO1-capped SUMO2/3 chain," Nature Communications, Nature, vol. 10(1), pages 1-12, December.
    5. Emma Branigan & J. Carlos Penedo & Ronald T. Hay, 2020. "Ubiquitin transfer by a RING E3 ligase occurs from a closed E2~ubiquitin conformation," Nature Communications, Nature, vol. 11(1), pages 1-11, December.
    6. Loes van Cuijk & Gijsbert J. van Belle & Yasemin Turkyilmaz & Sara L. Poulsen & Roel C. Janssens & Arjan F. Theil & Mariangela Sabatella & Hannes Lans & Niels Mailand & Adriaan B. Houtsmuller & Wim Ve, 2015. "SUMO and ubiquitin-dependent XPC exchange drives nucleotide excision repair," Nature Communications, Nature, vol. 6(1), pages 1-10, November.
    7. FangFang Zhou & Yvette Drabsch & Tim J. A. Dekker & Amaya Garcia de Vinuesa & Yihao Li & Lukas J. A. C. Hawinkels & Kelly-Ann Sheppard & Marie-José Goumans & Rodney B. Luwor & Carlie J. de Vries & Wil, 2014. "Nuclear receptor NR4A1 promotes breast cancer invasion and metastasis by activating TGF-β signalling," Nature Communications, Nature, vol. 5(1), pages 1-13, May.
    8. Helge M. Magnussen & Syed F. Ahmed & Gary. J. Sibbet & Ventzislava A. Hristova & Koji Nomura & Andreas K. Hock & Lewis J. Archibald & Andrew G. Jamieson & David Fushman & Karen H. Vousden & Allan M. W, 2020. "Structural basis for DNA damage-induced phosphoregulation of MDM2 RING domain," Nature Communications, Nature, vol. 11(1), pages 1-15, December.
    9. Gregory D Friedland & Nils-Alexander Lakomek & Christian Griesinger & Jens Meiler & Tanja Kortemme, 2009. "A Correspondence Between Solution-State Dynamics of an Individual Protein and the Sequence and Conformational Diversity of its Family," PLOS Computational Biology, Public Library of Science, vol. 5(5), pages 1-16, May.
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