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Science. 2016 Feb 19;351(6275). pii: aad9421. doi: 10.1126/science.aad9421.

Rpn1 provides adjacent receptor sites for substrate binding and deubiquitination by the proteasome.

Author information

1
Department of Cell Biology, Harvard Medical School, 240 Longwood Avenue, Boston, MA 02115, USA.
2
Protein Processing Section, Structural Biophysics Laboratory, Center for Cancer Research, National Cancer Institute, Frederick, MD 21702, USA.
3
Department of Chemistry and Chemical Biology, Northeastern University, Boston, MA 02115, USA.
4
Protein Processing Section, Structural Biophysics Laboratory, Center for Cancer Research, National Cancer Institute, Frederick, MD 21702, USA. Department of Analytical Chemistry, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, P. R. China.
5
Department of Analytical Chemistry, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, P. R. China.
6
Protein Processing Section, Structural Biophysics Laboratory, Center for Cancer Research, National Cancer Institute, Frederick, MD 21702, USA. Linganore High School, Frederick, MD 21701, USA.
7
Biophysics Resource, Structural Biophysics Laboratory, Center for Cancer Research, National Cancer Institute, Frederick, MD 21702, USA.
8
Department of Chemistry and Chemical Biology, Northeastern University, Boston, MA 02115, USA. j.engen@neu.edu kylie.walters@nih.gov daniel_finley@hms.harvard.edu.
9
Department of Cell Biology, Harvard Medical School, 240 Longwood Avenue, Boston, MA 02115, USA. j.engen@neu.edu kylie.walters@nih.gov daniel_finley@hms.harvard.edu.
10
Protein Processing Section, Structural Biophysics Laboratory, Center for Cancer Research, National Cancer Institute, Frederick, MD 21702, USA. j.engen@neu.edu kylie.walters@nih.gov daniel_finley@hms.harvard.edu.

Abstract

Hundreds of pathways for degradation converge at ubiquitin recognition by a proteasome. Here, we found that the five known proteasomal ubiquitin receptors in yeast are collectively nonessential for ubiquitin recognition and identified a sixth receptor, Rpn1. A site ( T1: ) in the Rpn1 toroid recognized ubiquitin and ubiquitin-like ( UBL: ) domains of substrate shuttling factors. T1 structures with monoubiquitin or lysine 48 diubiquitin show three neighboring outer helices engaging two ubiquitins. T1 contributes a distinct substrate-binding pathway with preference for lysine 48-linked chains. Proximal to T1 within the Rpn1 toroid is a second UBL-binding site ( T2: ) that assists in ubiquitin chain disassembly, by binding the UBL of deubiquitinating enzyme Ubp6. Thus, a two-site recognition domain intrinsic to the proteasome uses distinct ubiquitin-fold ligands to assemble substrates, shuttling factors, and a deubiquitinating enzyme.

PMID:
26912900
PMCID:
PMC4980823
DOI:
10.1126/science.aad9421
[Indexed for MEDLINE]
Free PMC Article

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