1. Institute of Biochemistry II and Cluster of Excellence Macromolecular Complexes, Goethe University, Theodor-Stern-Kai 7, D-60590 Frankfurt (Main), Germany
2. Tumor Biology Program, Mediterranean Institute for Life Sciences, Mestrovicevo setaliste, 21000 Split, Croatia
3. Department of Cell Biology, Harvard Medical School, 240 Longwood Avenue, Boston, Massachsuetts 02115, USA
4. Department of Biochemistry, Molecular Biology and Biophysics, University of Minnesota, Minneapolis, Minnesota 55455, USA
5. Miltenyi Biotec GmbH, Stoeckheimer Weg 1, D-50829 Koeln, Germany
6. Department of Immunology, Medical School University of Split, Soltanska 2, 21000 Split, Croatia
7. These authors contributed equally to this work.

Correspondence to: Kylie J. Walters⁴Daniel Finley³Ivan Dikic^1,2,6 Correspondence and requests for materials should be addressed to I.D. (Email: Ivan.Dikic@biochem2.de), D.F. (Email: daniel_finley@hms.harvard.edu), or K.J.W. (Email: walte048@umn.edu).

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.

1. Institute of Biochemistry II and Cluster of Excellence Macromolecular Complexes, Goethe University, Theodor-Stern-Kai 7, D-60590 Frankfurt (Main), Germany
2. Tumor Biology Program, Mediterranean Institute for Life Sciences, Mestrovicevo setaliste, 21000 Split, Croatia
3. Department of Cell Biology, Harvard Medical School, 240 Longwood Avenue, Boston, Massachsuetts 02115, USA
4. Department of Biochemistry, Molecular Biology and Biophysics, University of Minnesota, Minneapolis, Minnesota 55455, USA
5. Miltenyi Biotec GmbH, Stoeckheimer Weg 1, D-50829 Koeln, Germany
6. Department of Immunology, Medical School University of Split, Soltanska 2, 21000 Split, Croatia
7. These authors contributed equally to this work.

Correspondence to: Kylie J. Walters⁴Daniel Finley³Ivan Dikic^1,2,6 Correspondence and requests for materials should be addressed to I.D. (Email: Ivan.Dikic@biochem2.de), D.F. (Email: daniel_finley@hms.harvard.edu), or K.J.W. (Email: walte048@umn.edu).

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