2Y6E

Structure of the D1D2 domain of USP4, the conserved catalytic domain

Summary for 2Y6E

• Entry DOI: 10.2210/pdb2y6e/pdb
• Descriptor: UBIQUITIN CARBOXYL-TERMINAL HYDROLASE 4, ZINC ION, SULFATE ION, ... (4 entities in total)
• Functional Keywords: hydrolase
• Biological source: HOMO SAPIENS (HUMAN)
• Cellular location: Cytoplasm : Q13107
• Total number of polymer chains: 6
• Total formula weight: 254459.11

Authors

Luna-Vargas, M.P.A.,Faesen, A.C.,van Dijk, W.J.,Rape, M.,Fish, A.,Sixma, T.K. (deposition date: 2011-01-20, release date: 2011-04-06, Last modification date: 2024-11-06)

Primary citation

Clerici, M.,Luna-Vargas, M.P.A.,Faesen, A.C.,Sixma, T.K.
The Dusp-Ubl Domain of Usp4 Enhances its Catalytic Efficiency by Promoting Ubiquitin Exchange.
Nat.Commun., 5:5399-, 2014

PubMed Abstract: Ubiquitin-specific protease USP4 is emerging as an important regulator of cellular pathways, including the TGF-β response, NF-κB signalling and splicing, with possible roles in cancer. Here we show that USP4 has its catalytic triad arranged in a productive conformation. Nevertheless, it requires its N-terminal DUSP-Ubl domain to achieve full catalytic turnover. Pre-steady-state kinetics measurements reveal that USP4 catalytic domain activity is strongly inhibited by slow dissociation of ubiquitin after substrate hydrolysis. The DUSP-Ubl domain is able to enhance ubiquitin dissociation, hence promoting efficient turnover. In a mechanism that requires all USP4 domains, binding of the DUSP-Ubl domain promotes a change of a switching loop near the active site. This 'allosteric regulation of product discharge' provides a novel way of regulating deubiquitinating enzymes that may have relevance for other enzyme classes.

PubMed: 25404403
DOI: 10.1038/NCOMMS6399

Experimental method

X-RAY DIFFRACTION (2.4 Å)