PDBsum entry 5k1b

Protein binding/hydrolase

PDB id: 5k1b

Contents

Protein chains

579 a.a.

264 a.a.

Metals

_ZN

PDB id:

5k1b

Name:

Protein binding/hydrolase

Title:

Crystal structure of the uaf1/usp12 complex in f222 space group

Structure:

Wd repeat-containing protein 48. Chain: b. Synonym: usp1-associated factor 1,wd repeat endosomal protein,p80. Engineered: yes. Ubiquitin carboxyl-terminal hydrolase 12. Chain: a. Synonym: deubiquitinating enzyme 12,ubiquitin thioesterase 12, ubiquitin-hydrolyzing enzyme 1,ubiquitin-specific-processing protease 12.

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: wdr48, kiaa1449, uaf1. Expressed in: escherichia coli k-12. Expression_system_taxid: 83333. Gene: usp12, ubh1, usp12l1. Expression_system_taxid: 83333

Resolution:

3.30Å R-factor: 0.237 R-free: 0.286

Authors:

H.Li,A.D.D'Andrea,N.Zheng

Key ref:

H.Li et al. (2016). Allosteric Activation of Ubiquitin-Specific Proteases by β-Propeller Proteins UAF1 and WDR20. Mol Cell, 63, 249-260. PubMed id: 27373336 DOI: 10.1016/j.molcel.2016.05.031

Date:

18-May-16 Release date: 20-Jul-16

Protein chain

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

Seq: 677 a.a.

Struc: 579 a.a.

Protein chain

O75317  (UBP12_HUMAN) -  Ubiquitin carboxyl-terminal hydrolase 12 from Homo sapiens

Seq: 370 a.a.

Struc: 264 a.a.

Enzyme reactions

• Enzyme class: Chain A: 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.2016.05.031

Mol Cell 63:249-260 (2016)

PubMed id: 27373336

Allosteric Activation of Ubiquitin-Specific Proteases by β-Propeller Proteins UAF1 and WDR20.

H.Li, K.S.Lim, H.Kim, T.R.Hinds, U.Jo, H.Mao, C.E.Weller, J.Sun, C.Chatterjee, A.D.D'Andrea, N.Zheng.

ABSTRACT

Ubiquitin-specific proteases (USPs) constitute the largest family of deubiquitinating enzymes, whose catalytic competency is often modulated by their binding partners through unknown mechanisms. Here we report on a series of crystallographic and biochemical analyses of an evolutionarily conserved deubiquitinase, USP12, which is activated by two β-propeller proteins, UAF1 and WDR20. Our structures reveal that UAF1 and WDR20 interact with USP12 at two distinct sites far from its catalytic center. Without increasing the substrate affinity of USP12, the two β-propeller proteins potentiate the enzyme through different allosteric mechanisms. UAF1 docks at the distal end of the USP12 Fingers domain and induces a cascade of structural changes that reach a critical ubiquitin-contacting loop adjacent to the catalytic cleft. By contrast, WDR20 anchors at the base of this loop and remotely modulates the catalytic center of the enzyme. Our results provide a mechanistic example for allosteric activation of USPs by their regulatory partners.