PDBsum entry 6heh

Hydrolase

PDB id: 6heh

Contents

Protein chain

339 a.a.

Ligands

EDO

Metals

_CL

Waters ×128

PDB id:

6heh

Name:

Hydrolase

Title:

Structure of the catalytic domain of usp28 (insertion deleted)

Structure:

Ubiquitin carboxyl-terminal hydrolase 28,ubiquitin carboxyl-terminal hydrolase 28. Chain: a. Synonym: deubiquitinating enzyme 28,ubiquitin thioesterase 28, ubiquitin-specific-processing protease 28,deubiquitinating enzyme 28, ubiquitin thioesterase 28,ubiquitin-specific-processing protease 28. Engineered: yes. Mutation: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: usp28, kiaa1515. Expressed in: escherichia coli bl21(de3). Expression_system_taxid: 469008. Expression_system_variant: rosetta2 placi

Resolution:

2.26Å R-factor: 0.197 R-free: 0.216

Authors:

M.Gersch,D.Komander

Key ref:

M.Gersch et al. (2019). Distinct USP25 and USP28 Oligomerization States Regulate Deubiquitinating Activity. Mol Cell, 74, 436. PubMed id: 30926242 DOI: 10.1016/j.molcel.2019.02.030

Date:

20-Aug-18 Release date: 27-Mar-19

Protein chain

Q96RU2  (UBP28_HUMAN) -  Ubiquitin carboxyl-terminal hydrolase 28 from Homo sapiens

Seq: 1077 a.a.

Struc: 339 a.a.*

* PDB and UniProt seqs differ at 2 residue positions (black crosses)

Enzyme reactions

• Enzyme class: 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.molcel.2019.02.030

Mol Cell 74:436 (2019)

PubMed id: 30926242

Distinct USP25 and USP28 Oligomerization States Regulate Deubiquitinating Activity.

M.Gersch, J.L.Wagstaff, A.V.Toms, B.Graves, S.M.V.Freund, D.Komander.

ABSTRACT

The evolutionarily related deubiquitinating enzymes (DUBs) USP25 and USP28 comprise an identical overall domain architecture but are functionally non-redundant: USP28 stabilizes c-MYC and other nuclear proteins, and USP25 regulates inflammatory TRAF signaling. We here compare molecular features of USP25 and USP28. Active enzymes form distinctively shaped dimers, with a dimerizing insertion spatially separating independently active catalytic domains. In USP25, but not USP28, two dimers can form an autoinhibited tetramer, where a USP25-specific, conserved insertion sequence blocks ubiquitin binding. In full-length enzymes, a C-terminal domain with a previously unknown fold has no impact on oligomerization, but N-terminal regions affect the dimer-tetramer equilibrium in vitro. We confirm oligomeric states of USP25 and USP28 in cells and show that modulating oligomerization affects substrate stabilization in accordance with in vitro activity data. Our work highlights how regions outside of the catalytic domain enable a conceptually intriguing interplay of DUB oligomerization and activity.