PDBsum entry 5ctr

Immune system, nuclear protein, RNA bind

PDB id: 5ctr

Contents

Protein chains

308 a.a.

206 a.a.

Waters ×39

PDB id:

5ctr

Name:

Immune system, nuclear protein, RNA bind

Title:

Crystal structure of human sart3 hat-c domain-human usp4 dusp-ubl domain complex

Structure:

Squamous cell carcinoma antigen recognized by t-cells 3. Chain: a, b. Fragment: unp residues 278-611. Synonym: sart-3,tat-interacting protein of 110 kda,tip110,p110 nuclear RNA-binding protein. Engineered: yes. Ubiquitin carboxyl-terminal hydrolase 4. Chain: c, d. Fragment: unp residues 1-230.

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: sart3, kiaa0156, tip110. Expressed in: escherichia coli. Expression_system_taxid: 562. Gene: usp4, unp, unph. Expression_system_taxid: 562

Resolution:

3.01Å R-factor: 0.310 R-free: 0.334

Authors:

J.K.Park,E.E.Kim

Key ref:

J.K.Park et al. (2016). Structural basis for recruiting and shuttling of the spliceosomal deubiquitinase USP4 by SART3. Nucleic Acids Res, 44, 5424-5437. PubMed id: 27060135 DOI: 10.1093/nar/gkw218

Date:

24-Jul-15 Release date: 27-Apr-16

Protein chains

Q15020  (SART3_HUMAN) -  Squamous cell carcinoma antigen recognized by T-cells 3 from Homo sapiens

Seq: 963 a.a.

Struc: 308 a.a.

Protein chains

Q13107  (UBP4_HUMAN) -  Ubiquitin carboxyl-terminal hydrolase 4 from Homo sapiens

Seq: 963 a.a.

Struc: 206 a.a.

Enzyme reactions

• Enzyme class: Chains C, D: 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: 10.1093/nar/gkw218

Nucleic Acids Res 44:5424-5437 (2016)

PubMed id: 27060135

Structural basis for recruiting and shuttling of the spliceosomal deubiquitinase USP4 by SART3.

J.K.Park, T.Das, E.J.Song, E.E.Kim.

ABSTRACT

Squamous cell carcinoma antigen recognized by T-cells 3 (SART3) is a U4/U6 recycling factor as well as a targeting factor of USP4 and USP15. However, the details of how SART3 recognizes these deubiquitinases and how they get subsequently translocated into the nucleus are not known. Here, we present the crystal structures of the SART3 half-a-tetratricopeptide (HAT) repeat domain alone and in complex with the domain present in ubiquitin-specific protease (DUSP)-ubiquitin-like (UBL) domains of ubiquitin specific protease 4 (USP4). The 12 HAT repeats of SART3 are in two sub-domains (HAT-N and HAT-C) forming a dimer through HAT-C. USP4 binds SART3 at the opposite surface of the HAT-C dimer interface utilizing the β-structured linker between the DUSP and the UBL domains. The binding affinities of USP4 and USP15 to SART3 are 0.9 μM and 0.2 μM, respectively. The complex structure of SART3 nuclear localization signal (NLS) and importin-α reveals bipartite binding, and removal of SART3 NLS prevents the entry of USP4 (and USP15) into the nucleus and abrogates the subsequent deubiquitinase activity of USP4.