3TMP

The catalytic domain of human deubiquitinase DUBA in complex with ubiquitin aldehyde

Summary for 3TMP

• Entry DOI: 10.2210/pdb3tmp/pdb
• Related: 3TMO
• Descriptor: OTU domain-containing protein 5, Polyubiquitin-C (3 entities in total)
• Functional Keywords: otu fold, deubiquitinase, phosphorylation, hydrolase-protein binding complex, hydrolase/protein binding
• Biological source: Homo sapiens (human); More
• Cellular location: Ubiquitin: Cytoplasm (By similarity): P0CG48
• Total number of polymer chains: 8
• Total formula weight: 119269.44

Authors

Ma, X.,Yin, J.,Hymowitz, S.,Starovasnik, M.,Cochran, A. (deposition date: 2011-08-31, release date: 2012-01-11, Last modification date: 2025-03-26)

Primary citation

Huang, O.W.,Ma, X.,Yin, J.,Flinders, J.,Maurer, T.,Kayagaki, N.,Phung, Q.,Bosanac, I.,Arnott, D.,Dixit, V.M.,Hymowitz, S.G.,Starovasnik, M.A.,Cochran, A.G.
Phosphorylation-dependent activity of the deubiquitinase DUBA.
Nat.Struct.Mol.Biol., 19:171-175, 2012

PubMed Abstract: Addition and removal of ubiquitin or ubiquitin chains to and from proteins is a tightly regulated process that contributes to cellular signaling and protein stability. Here we show that phosphorylation of the human deubiquitinase DUBA (OTUD5) at a single residue, Ser177, is both necessary and sufficient to activate the enzyme. The crystal structure of the ubiquitin aldehyde adduct of active DUBA reveals a marked cooperation between phosphorylation and substrate binding. An intricate web of interactions involving the phosphate and the C-terminal tail of ubiquitin cause DUBA to fold around its substrate, revealing why phosphorylation is essential for deubiquitinase activity. Phosphoactivation of DUBA represents an unprecedented mode of protease regulation and a clear link between two major cellular signal transduction systems: phosphorylation and ubiquitin modification.

PubMed: 22245969
DOI: 10.1038/nsmb.2206

Experimental method

X-RAY DIFFRACTION (1.91 Å)