Proteasome subunit Rpn13 is a novel ubiquitin receptor

• Published in: Nature 2008-05, Vol.453 (7194), p.481-488
• Main Authors: Walters, Kylie J, Finley, Daniel, Dikic, Ivan, Husnjak, Koraljka, Elsasser, Suzanne, Zhang, Naixia, Chen, Xiang, Randles, Leah, Shi, Yuan, Hofmann, Kay
• Format: Article
• Language: English
• Subjects: Amino Acid Sequence; Animals; Binding Sites - genetics; Biodegradation; Biological and medical sciences; Cell Adhesion Molecules - chemistry; Cell Adhesion Molecules - genetics; Cell Adhesion Molecules - metabolism; Cell receptors; Cell structures and functions; Fundamental and applied biological sciences. Psychology; Genetic aspects; Humanities and Social Sciences; Humans; Intracellular Signaling Peptides and Proteins; Membrane Glycoproteins - chemistry; Membrane Glycoproteins - genetics; Membrane Glycoproteins - metabolism; Mice; Miscellaneous; Molecular and cellular biology; Molecular Sequence Data; multidisciplinary; Mutation - genetics; Phenotype; Proteasome Endopeptidase Complex - chemistry; Proteasome Endopeptidase Complex - genetics; Proteasome Endopeptidase Complex - metabolism; Protein Subunits - chemistry; Protein Subunits - genetics; Protein Subunits - metabolism; Proteins; Saccharomyces cerevisiae Proteins - chemistry; Saccharomyces cerevisiae Proteins - genetics; Saccharomyces cerevisiae Proteins - metabolism; Science; Science (multidisciplinary); Substrates; Ubiquitin - metabolism; Ubiquitin-proteasome system; Yeast fungi; Yeasts
• ISSN: 0028-0836; 1476-4687; 1476-4679
• DOI: 10.1038/nature06926

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. Proteasomes: Ubiquitin binding via Rpn 13 The 26S proteasome is a multisubunit complex that selectively degrades ubiquitin conjugated proteins. Two studies show that a known component of the proteasome, Rpn13 functions as a novel ubiquitin binding receptor. Structural studies reveal a novel mode of ubiquitin recognition. Rpn 13 is also a receptor for a deubiquitinating enzyme, suggesting a linkage between ubiquitin chain recognition and disassembly. The 26S proteasome is a multisubunit complex that selectively degrades ubiquitin conjugated proteins. Two studies (this Article and the Letter Dikic doi:10.1038/nature06924) show that a known component of the proteasome, Rpn13, functions as a novel ubiquitin binding receptor, and structural studies reveal a novel mode of ubiquitin recognition. Rpn13 is also a receptor for a deubiquitinating enzyme, suggesting a linkage between ubiquitin chain recognition and disassembly.