論文 - 詳細
| RRC ID | 47938 |
|---|---|
| 著者 | Kawaguchi K, Uo K, Tanaka T, Komada M. |
| タイトル | Tandem UIMs confer Lys48 ubiquitin chain substrate preference to deubiquitinase USP25. |
| ジャーナル | Sci Rep |
| Abstract |
Ubiquitin-specific protease (USP) 25, belonging to the USP family of deubiquitinases, harbors two tandem ubiquitin-interacting motifs (UIMs), a ~20-amino-acid α-helical stretch that binds to ubiquitin. However, the role of the UIMs in USP25 remains unclear. Here we show that the tandem UIM region binds to Lys48-, but not Lys63-, linked ubiquitin chains, where the two UIMs played a critical and cooperative role. Purified USP25 exhibited higher ubiquitin isopeptidase activity to Lys48-, than to Lys63-, linked ubiquitin chains. Mutations that disrupted the ubiquitin-binding ability of the tandem UIMs resulted in a reduced ubiquitin isopeptidase activity of USP25, suggesting a role for the UIMs in exerting the full catalytic activity of USP25. Moreover, when mutations that convert the binding preference from Lys48- to Lys63-linked ubiquitin chains were introduced into the tandem UIM region, the USP25 mutants acquired elevated and reduced isopeptidase activity toward Lys63- and Lys48-linked ubiquitin chains, respectively. These results suggested that the binding preference of the tandem UIMs toward Lys48-linked ubiquitin chains contributes not only to the full catalytic activity but also to the ubiquitin chain substrate preference of USP25, possibly by selectively holding the Lys48-linked ubiquitin chain substrates in the proximity of the catalytic core. |
| 巻・号 | 7 |
| ページ | 45037 |
| 公開日 | 2017-3-22 |
| DOI | 10.1038/srep45037 |
| PII | srep45037 |
| PMID | 28327663 |
| PMC | PMC5361193 |
| MeSH | Amino Acid Motifs* Amino Acid Sequence Binding Sites* Catalysis Cell Line Humans Lysine / metabolism* Models, Biological Peptide Hydrolases / metabolism Protein Binding Protein Interaction Domains and Motifs Substrate Specificity Ubiquitin / chemistry Ubiquitin / metabolism* Ubiquitin Thiolesterase / chemistry Ubiquitin Thiolesterase / genetics Ubiquitin Thiolesterase / metabolism* |
| IF | 3.998 |
| 引用数 | 7 |
| WOS 分野 | BIOCHEMISTRY & MOLECULAR BIOLOGY |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 最多言及媒体 | News |
| 各媒体での言及数の合計 | 4 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| 遺伝子材料 | Genome Network Project Human cDNA IRAK168O08 (HGY067544) |