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Molecular basis for bre5 cofactor recognition by the ubp3 deubiquitylating enzyme.

Yeast Ubp3 and its co-factor Bre5 form a deubiquitylation complex to regulate protein transport between the endoplasmic reticulum and Golgi compartments of the cell. A novel N-terminal domain of the Ubp3 catalytic subunit forms a complex with the NTF2-like domain of the Bre5 regulatory subunit. Here, we report the X-ray crystal structure of an Ubp3-Bre5 complex and show that it forms a symmetric hetero-tetrameric complex in which the Bre5 NTF2-like domain dimer interacts with two L-shaped beta-strand-turn-alpha-helix motifs of Ubp3. The Ubp3 N-terminal domain binds within a hydrophobic cavity on the surface of the Bre5 NTF2-like domain subunit with conserved residues within both proteins interacting predominantly through antiparallel beta-sheet hydrogen bonds and van der Waals contacts. Structure-based mutagenesis and functional studies confirm the significance of the observed interactions for Ubp3-Bre5 association in vitro and Ubp3 function in vivo. Comparison of the structure to other protein complexes with NTF2-like domains shows that the Ubp3-Bre5 interface is novel. Together, these studies provide new insights into Ubp3 recognition by Bre5 and into protein recognition by NTF2-like domains.

Pubmed ID: 17632125


  • Li K
  • Ossareh-Nazari B
  • Liu X
  • Dargemont C
  • Marmorstein R


Journal of molecular biology

Publication Data

September 7, 2007

Associated Grants

  • Agency: NCRR NIH HHS, Id: P41 RR012408
  • Agency: NCRR NIH HHS, Id: P41 RR012408-095406

Mesh Terms

  • Amino Acid Sequence
  • Binding Sites
  • Carrier Proteins
  • Coenzymes
  • Endopeptidases
  • Models, Molecular
  • Molecular Sequence Data
  • Mutagenesis, Site-Directed
  • Protein Binding
  • Protein Processing, Post-Translational
  • Protein Structure, Tertiary
  • Saccharomyces cerevisiae Proteins
  • Sequence Homology, Amino Acid
  • Ubiquitin