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-α, 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 α-helical bundle supporting a triple-stranded anti-parallel β-sheet. The DUSP domain displays a novel fold, an α/β tripod (AB3). DUSP domain surface properties and previously described work suggest a potential role in protein/protein interaction or substrate recognition. © 2006 by The American Society for Biochemistry and Molecular Biology, Inc.