Structure of a complex between Nedd8 and the Ulp/Senp protease family member Den1 |
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Authors: | Reverter David Wu Kenneth Erdene Tudeviin Gan Pan Zhen-Qiang Wilkinson Keith D Lima Christopher D |
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Institution: | Structural Biology Program, Sloan-Kettering Institute, New York, NY 10021, USA. |
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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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Keywords: | X-ray structure cysteine protease ubiquitin-like Nedd8 Ulp family |
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