Structure of a complex between Nedd8 and the Ulp/Senp protease family member Den1

David Reverter, Kenneth Wu, Tudeviin Gan Erdene, Zhen Qiang Pan, Keith D. Wilkinson, Christopher D. Lima

Research output: Contribution to journalArticlepeer-review

72 Scopus citations

Abstract

The Nedd8 conjugation pathway is conserved from yeast to humans and is essential in many organisms. Nedd8 is conjugated to cullin proteins in a process that alters SCF E3 ubiquitin ligase activity, and it is presumed that Nedd8 deconjugation would reverse these effects. We now report the X-ray structures of the human Nedd8-specific protease, Den1, in a complex with the inhibitor Nedd8 aldehyde, thus revealing a model for the tetrahedral transition state intermediate generated during proteolysis. Although Den1 is closely related to the SUMO-specific protease family (Ulp/Senp family), structural analysis of the interface suggests determinants involved in Nedd8 selectivity by Den1 over other ubiquitin-like family members and suggests how the Ulp/Senp architecture has been modified to interact with different ubiquitin-like modifiers.

Original languageEnglish
Pages (from-to)141-151
Number of pages11
JournalJournal of Molecular Biology
Volume345
Issue number1
DOIs
StatePublished - 7 Jan 2005

Keywords

  • Nedd8
  • Ulp family
  • X-ray structure
  • cysteine protease
  • ubiquitin-like

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