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Updated: Aug 14, 2026

Measuring Enzymatic Activity of Neurodevelopmental Disorder-Associated Deubiquitylating Enzymes via an In Vitro Ubiquitin Chain Cleavage Assay
Published on: September 27, 2024
Solution structure of the human ubiquitin-specific protease 15 DUSP domain
Rob N de Jong1, Eiso Ab, Tammo Diercks
1Department of NMR Spectroscopy, Bijvoet Center for Biomolecular Research, Utrecht University, Padualaan 8, 3584 CH Utrecht, The Netherlands.
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.
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