5CVN

WDR48 (2-580):USP46~ubiquitin ternary complex

Summary for 5CVN

• Entry DOI: 10.2210/pdb5cvn/pdb
• Related: 5CVL 5CVM 5CVO
• Descriptor: WD repeat-containing protein 48, Ubiquitin carboxyl-terminal hydrolase 46, Polyubiquitin-B, ... (5 entities in total)
• Functional Keywords: wdr48, wd repeat, beta propeller, usp46, ubiquitin, covalent complex, dub, deubiquitinase, hydrolase-protein binding complex, hydrolase/protein binding
• Biological source: Homo sapiens (Human); More
• Cellular location: Nucleus: Q8TAF3; Ubiquitin: Cytoplasm : P0CG47
• Total number of polymer chains: 3
• Total formula weight: 119924.08

Authors

Harris, S.F.,Yin, J. (deposition date: 2015-07-27, release date: 2015-10-07, Last modification date: 2024-11-06)

Primary citation

Yin, J.,Schoeffler, A.J.,Wickliffe, K.,Newton, K.,Starovasnik, M.A.,Dueber, E.C.,Harris, S.F.
Structural Insights into WD-Repeat 48 Activation of Ubiquitin-Specific Protease 46.
Structure, 23:2043-2054, 2015

PubMed Abstract: Protein ubiquitination patterns are an important component of cellular signaling. The WD-repeat protein WDR48 (USP1-associated factor UAF-1) stimulates activity of ubiquitin-specific proteases USP1, USP12, and USP46. To understand how WDR48 exerts its effect on the USP scaffold, we determined structures of the ternary WDR48:USP46:ubiquitin complex. WDR48 interacts with the USP46 fingers subdomain via a relatively small, highly polar surface on the top center of the WDR48 β propeller. In addition, WDR48 has a novel ancillary domain and a C-terminal SUMO-like domain encircling the USP46-bound ubiquitin. Mutation of residues involved in the WDR48:USP46 interaction abrogated both binding and deubiquitinase activity of the complex. An analogous mutation in USP1 similarly blocked WDR48-dependent activation. Our data suggest a possible mechanism of deubiquitinase stimulation via stabilization and prolonged residence time of substrate. The unprecedented mode of interaction between the USP fingers domain and the WD-repeat β propeller serves as a prototypical example for this family of deubiquitinases.

PubMed: 26388029
DOI: 10.1016/j.str.2015.08.010

Experimental method

X-RAY DIFFRACTION (3.36 Å)