PDBsum entry 5cvn

Hydrolase/protein binding

PDB id: 5cvn

Contents

Protein chains

514 a.a.

321 a.a.

76 a.a.

Metals

_ZN

Waters ×34

PDB id:

5cvn

Name:

Hydrolase/protein binding

Title:

Wdr48 (2-580):usp46~ubiquitin ternary complex

Structure:

Wd repeat-containing protein 48. Chain: a. Fragment: unp residues 2-580. Synonym: usp1-associated factor 1,wd repeat endosomal protein,p80. Engineered: yes. Ubiquitin carboxyl-terminal hydrolase 46. Chain: b. Fragment: unp residues 25-366. Synonym: deubiquitinating enzyme 46,ubiquitin thioesterase 46,

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: wdr48, kiaa1449, uaf1. Expressed in: trichoplusia ni. Expression_system_taxid: 7111. Gene: usp46. Gene: ubb.

Resolution:

3.36Å R-factor: 0.177 R-free: 0.222

Authors:

S.F.Harris,J.Yin

Key ref:

J.Yin et al. (2015). Structural Insights into WD-Repeat 48 Activation of Ubiquitin-Specific Protease 46. Structure, 23, 2043-2054. PubMed id: 26388029 DOI: 10.1016/j.str.2015.08.010

Date:

27-Jul-15 Release date: 07-Oct-15

Protein chain

Q8TAF3  (WDR48_HUMAN) -  WD repeat-containing protein 48 from Homo sapiens

Seq: 677 a.a.

Struc: 514 a.a.

Protein chain

P62068  (UBP46_HUMAN) -  Ubiquitin carboxyl-terminal hydrolase 46 from Homo sapiens

Seq: 366 a.a.

Struc: 321 a.a.

Protein chain

P0CG47  (UBB_HUMAN) -  Polyubiquitin-B from Homo sapiens

Seq: 229 a.a.

Struc: 76 a.a.

Enzyme reactions

• Enzyme class: Chain B: E.C.3.4.19.12 - ubiquitinyl hydrolase 1.
• Reaction: Thiol-dependent hydrolysis of ester, thiolester, amide, peptide and isopeptide bonds formed by the C-terminal Gly of ubiquitin (a 76-residue protein attached to proteins as an intracellular targeting signal).

DOI no: 10.1016/j.str.2015.08.010

Structure 23:2043-2054 (2015)

PubMed id: 26388029

Structural Insights into WD-Repeat 48 Activation of Ubiquitin-Specific Protease 46.

J.Yin, A.J.Schoeffler, K.Wickliffe, K.Newton, M.A.Starovasnik, E.C.Dueber, S.F.Harris.

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.