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
リソース情報
遺伝子材料 Genome Network Project Human cDNA IRAK168O08 (HGY067544)