title: Solution structure of the human ubiquitin-specific protease 15 DUSP domain.
abstract: Ubiquitin-specific proteases (USPs) can remove covalently attached ubiquitin moieties from target proteins and regulate both the stability and ubiquitin-signaling state of their substrates. All USPs contain a conserved catalytic domain surrounded by one or more subdomains, some of which contribute to target recognition. One such specific subdomain, the DUSP domain (domain present in ubiquitin-specific proteases), is present in at least seven different human USPs that regulate the stability of or interact with the hypoxia-inducible transcription factor HIF1-alpha, the Von Hippel-Lindau protein (pVHL), cullin E3 ligases, and BRCA2. We describe the NMR solution structure of the DUSP domain of human USP15, recently implicated in COP9 (constitutive photomorphogenic gene 9)-signalosome regulation. Its tripod-like structure consists of a 3-fold alpha-helical bundle supporting a triple-stranded anti-parallel beta-sheet. The DUSP domain displays a novel fold, an alpha/beta tripod (AB3). DUSP domain surface properties and previously described work suggest a potential role in protein/protein interaction or substrate recognition.
authors.affiliation: Department of NMR Spectroscopy, Bijvoet Center for Biomolecular Research, Utrecht University, Padualaan 8, 3584 CH Utrecht, The Netherlands.
authors.forename: Rob N
authors.initials: RN
authors.lastname: de Jong
authors.forename: Eiso
authors.initials: E
authors.lastname: Ab
authors.forename: Tammo
authors.initials: T
authors.lastname: Diercks
authors.forename: Vincent
authors.initials: V
authors.lastname: Truffault
authors.forename: Mark
authors.initials: M
authors.lastname: Daniëls
authors.forename: Robert
authors.initials: R
authors.lastname: Kaptein
authors.forename: Gert E
authors.initials: GE
authors.lastname: Folkers
mesh_terms: D000595:Amino Acid Sequence; D024682:BRCA2 Protein / Q000378:metabolism; D020134:Catalytic Domain; D044842:Cullin Proteins / Q000737:chemistry; D018076:DNA, Complementary / Q000378:metabolism; D010450:Endopeptidases / Q000737:chemistry* / Q000378:metabolism; D005786:Gene Expression Regulation; D015723:Gene Library; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011487:Protein Conformation; D017510:Protein Folding; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D017386:Sequence Homology, Amino Acid; D025801:Ubiquitin / Q000737:chemistry*; D044767:Ubiquitin-Protein Ligases / Q000378:metabolism; D064570:Ubiquitin-Specific Proteases; D051794:Von Hippel-Lindau Tumor Suppressor Protein / Q000378:metabolism
chemical_list: D024682:BRCA2 Protein; D044842:Cullin Proteins; D018076:DNA, Complementary; C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D025801:Ubiquitin; D044767:Ubiquitin-Protein Ligases; D051794:Von Hippel-Lindau Tumor Suppressor Protein; D010450:Endopeptidases; C579226:USP15 protein, human; D064570:Ubiquitin-Specific Proteases; C497446:VHL protein, human