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Updated: Aug 20, 2026

Detection of Protein Ubiquitination
Published on: August 19, 2009
Structure of a complex between Nedd8 and the Ulp/Senp protease family member Den1
David Reverter1, Kenneth Wu, Tudeviin Gan Erdene
1Structural Biology Program, Sloan-Kettering Institute, New York, NY 10021, USA.
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.
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