Solution structure of the human ubiquitin-specific protease 15 DUSP domain

J Biol Chem. 2006 Feb 24;281(8):5026-31. doi: 10.1074/jbc.M510993200. Epub 2005 Nov 18.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • BRCA2 Protein / metabolism
  • Catalytic Domain
  • Cullin Proteins / chemistry
  • DNA, Complementary / metabolism
  • Endopeptidases / chemistry*
  • Endopeptidases / metabolism
  • Gene Expression Regulation*
  • Gene Library
  • Humans
  • Hypoxia-Inducible Factor 1, alpha Subunit / metabolism
  • Magnetic Resonance Spectroscopy
  • Models, Molecular
  • Molecular Sequence Data
  • Protein Conformation
  • Protein Folding
  • Protein Structure, Secondary
  • Protein Structure, Tertiary
  • Sequence Homology, Amino Acid
  • Ubiquitin / chemistry*
  • Ubiquitin-Protein Ligases / metabolism
  • Ubiquitin-Specific Proteases
  • Von Hippel-Lindau Tumor Suppressor Protein / metabolism


  • BRCA2 Protein
  • Cullin Proteins
  • DNA, Complementary
  • HIF1A protein, human
  • Hypoxia-Inducible Factor 1, alpha Subunit
  • Ubiquitin
  • Ubiquitin-Protein Ligases
  • Von Hippel-Lindau Tumor Suppressor Protein
  • Endopeptidases
  • USP15 protein, human
  • Ubiquitin-Specific Proteases
  • VHL protein, human

Associated data

  • PDB/1W6V