Back to Search
Start Over
Phosphorylation-dependent activity of the deubiquitinase DUBA.
- Source :
- Nature Structural & Molecular Biology; Feb2012, Vol. 19 Issue 2, p171-175, 5p, 1 Black and White Photograph, 1 Diagram, 1 Chart, 2 Graphs
- Publication Year :
- 2012
-
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. [ABSTRACT FROM AUTHOR]
- Subjects :
- PHOSPHORYLATION
UBIQUITIN
PROTEINS
ENZYMES
CRYSTAL structure
Subjects
Details
- Language :
- English
- ISSN :
- 15459993
- Volume :
- 19
- Issue :
- 2
- Database :
- Complementary Index
- Journal :
- Nature Structural & Molecular Biology
- Publication Type :
- Academic Journal
- Accession number :
- 71519822
- Full Text :
- https://doi.org/10.1038/nsmb.2206