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Structure of Rpn10 and Its Interactions with Polyubiquitin Chains and the Proteasome Subunit Rpn12 |
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| Authors: | Christiane Riedinger Jonas Boehringer Jean-Francois Trempe Edward D Lowe Nicholas R Brown Kalle Gehring Martin E M Noble Colin Gordon and Jane A Endicott |
| Institution: | From the ‡Laboratory of Molecular Biophysics, Department of Biochemistry, University of Oxford, South Parks Road, Oxford OX1 3QU, United Kingdom, ;the §Department of Biochemistry, McGill University, 3655 Promenade Sir William Osler, Montreal, Quebec H3G 1Y6, Canada, and ;the ¶Medical Research Council Human Genetics Unit, Western General Hospital, Crewe Road, Edinburgh EH4 2XU, Scotland, United Kingdom |
| Abstract: | Schizosaccharomyces pombe Rpn10 (SpRpn10) is a proteasomal ubiquitin (Ub) receptor located within the 19 S regulatory particle where it binds to subunits of both the base and lid subparticles. We have solved the structure of full-length SpRpn10 by determining the crystal structure of the von Willebrand factor type A domain and characterizing the full-length protein by NMR. We demonstrate that the single Ub-interacting motif (UIM) of SpRpn10 forms a 1:1 complex with Lys48-linked diUb, which it binds selectively over monoUb and Lys63-linked diUb. We further show that the SpRpn10 UIM binds to SpRpn12, a subunit of the lid subparticle, with an affinity comparable with Lys48-linked diUb. This is the first observation of a UIM binding other than a Ub fold and suggests that SpRpn12 could modulate the activity of SpRpn10 as a proteasomal Ub receptor. |
| Keywords: | Biophysics NMR Proteasome Signal Transduction Ubiquitin X-ray Crystallography |