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RBR ligase–mediated ubiquitin transfer: a tale with many twists and turns

Nature Structural & Molecular Biology volume 25, pages 440–445 (2018)Cite this article

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Abstract

RBR ligases are an enigmatic class of E3 ubiquitin ligases that combine properties of RING and HECT-type E3s and undergo multilevel regulation through autoinhibition, post-translational modifications, multimerization and interaction with binding partners. Here, we summarize recent progress in RBR structures and function, which has uncovered commonalities in the mechanisms by which different family members transfer ubiquitin through a multistep process. However, these studies have also highlighted clear differences in the activity of different family members, suggesting that each RBR ligase has evolved specific properties to fit the biological process it regulates.

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Fig. 1: The catalytic cycle of RBR ligases.
Fig. 2: Domain arrangement during autoinhibition and in the active state of RBRs.
Fig. 3: Multiple Ub and Ubl-binding sites determine the activity of RBRs.

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Acknowledgements

This work was supported by the Medical Research Council (MRC grant number MC_UU_12016/12) and the European Research Council (ERC-2015-CoG-681582 ICLUb consolidator grant) to H.W. and by the Francis Crick Institute which receives its core funding from Cancer Research UK (FC001142), the UK Medical Research Council (FC001142), and the Wellcome Trust (FC001142) to K.R. We acknowledge V. Chaugule, C. Arkinson and L. Martino for helpful discussions.

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  1. Institute of Molecular Cell and Systems Biology, University of Glasgow, Glasgow, Scotland, UK

    Helen Walden

  2. Molecular Structure of Cell Signalling Laboratory, The Francis Crick Institute, London, UK

    Katrin Rittinger

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Correspondence to Helen Walden or Katrin Rittinger.

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Walden, H., Rittinger, K. RBR ligase–mediated ubiquitin transfer: a tale with many twists and turns. Nat Struct Mol Biol 25, 440–445 (2018). https://doi.org/10.1038/s41594-018-0063-3

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