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Proteasome subunit Rpn13 is a novel ubiquitin receptor

Nature volume 453, pages 481–488 (2008)Cite this article

Abstract

Proteasomal receptors that recognize ubiquitin chains attached to substrates are key mediators of selective protein degradation in eukaryotes. Here we report the identification of a new ubiquitin receptor, Rpn13/ARM1, a known component of the proteasome. Rpn13 binds ubiquitin through a conserved amino-terminal region termed the pleckstrin-like receptor for ubiquitin (Pru) domain, which binds K48-linked diubiquitin with an affinity of approximately 90 nM. Like proteasomal ubiquitin receptor Rpn10/S5a, Rpn13 also binds ubiquitin-like (UBL) domains of UBL-ubiquitin-associated (UBA) proteins. In yeast, a synthetic phenotype results when specific mutations of the ubiquitin binding sites of Rpn10 and Rpn13 are combined, indicating functional linkage between these ubiquitin receptors. Because Rpn13 is also the proteasomal receptor for Uch37, a deubiquitinating enzyme, our findings suggest a coupling of chain recognition and disassembly at the proteasome.

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Figure 1: Murine Rpn13 binds ubiquitin chains.
Figure 2: Rpn13 contributes to recognition of ubiquitin conjugates by the proteasome.
Figure 3: Rpn13 uses loops to bind ubiquitin.
Figure 4: Rpn13 binds to ubiquitin and UBLs of proteasomal receptors.
Figure 5: An Rpn13 mutant specifically defective in ubiquitin chain binding.
Figure 6: Phenotypic effects of the loss of ubiquitin receptor function by Rpn13.

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Accession codes

Primary accessions

Protein Data Bank

Data deposits

The structures of full-length scRpn13 are deposited in Protein Data Bank under accession number 2Z4D.

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Acknowledgements

We thank members of our laboratories, as well as D. Hoeller, G. Dittmar, J. Lipscomb and M. Schmidt, for discussions, comments and reading of the manuscript. We also thank the University of Minnesota’s NMR facility, Minnesota Supercomputing Institutes’s Basic Sciences Computing Laboratory and E. Arriaga for allowing us to use his spectrofluorometer. We thank G. Zapart for the initial Y2H ubiquitin screening, and M. Groll and P. Schneider for allowing us to use the mRpn13–ubiquitin coordinates to generate Fig. 5c. This work was supported by grants from Deutsche Forschungsgemeinschaft (DI 931/3-1), the Cluster of Excellence ‘Macromolecular Complexes’ of the Goethe University Frankfurt (EXC115) (I.D.) and the National Institutes of Health (CA097004 to K.J.W.; GM043601 to D.F.; GM008700-CBITG to L.R.).

Author information

Author notes

  1. Koraljka Husnjak, Suzanne Elsasser and Naixia Zhang: These authors contributed equally to this work.

Authors and Affiliations

  1. Institute of Biochemistry II and Cluster of Excellence Macromolecular Complexes, Goethe University, Theodor-Stern-Kai 7, D-60590 Frankfurt (Main), Germany ,

    Koraljka Husnjak & Ivan Dikic

  2. Tumor Biology Program, Mediterranean Institute for Life Sciences, Mestrovicevo setaliste, 21000 Split, Croatia ,

    Koraljka Husnjak & Ivan Dikic

  3. Department of Cell Biology, Harvard Medical School, 240 Longwood Avenue, Boston, Massachsuetts 02115, USA,

    Suzanne Elsasser, Yuan Shi & Daniel Finley

  4. Department of Biochemistry, Molecular Biology and Biophysics, University of Minnesota, Minneapolis, Minnesota 55455, USA,

    Naixia Zhang, Xiang Chen, Leah Randles & Kylie J. Walters

  5. Miltenyi Biotec GmbH, Stoeckheimer Weg 1, D-50829 Koeln, Germany ,

    Kay Hofmann

  6. Department of Immunology, Medical School University of Split, Soltanska 2, 21000 Split, Croatia,

    Ivan Dikic

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  1. Koraljka Husnjak
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Correspondence to Kylie J. Walters, Daniel Finley or Ivan Dikic.

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Husnjak, K., Elsasser, S., Zhang, N. et al. Proteasome subunit Rpn13 is a novel ubiquitin receptor. Nature 453, 481–488 (2008). https://doi.org/10.1038/nature06926

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