5CTR

Crystal structure of human SART3 HAT-C domain-human USP4 DUSP-UBL domain complex

Summary for 5CTR

• Entry DOI: 10.2210/pdb5ctr/pdb
• Related: 5CTQ 5CTT
• Descriptor: Squamous cell carcinoma antigen recognized by T-cells 3, Ubiquitin carboxyl-terminal hydrolase 4 (3 entities in total)
• Functional Keywords: nuclear complex, deubiquitinase, immune system, nuclear protein, rna binding protein, hydrolase
• Biological source: Homo sapiens (Human); More
• Cellular location: Nucleus, nucleoplasm : Q15020; Cytoplasm : Q13107
• Total number of polymer chains: 4
• Total formula weight: 133861.57

Authors

Park, J.K.,Kim, E.E. (deposition date: 2015-07-24, release date: 2016-04-27, Last modification date: 2024-10-23)

Primary citation

Park, J.K.,Das, T.,Song, E.J.,Kim, E.E.
Structural basis for recruiting and shuttling of the spliceosomal deubiquitinase USP4 by SART3
Nucleic Acids Res., 44:5424-5437, 2016

PubMed 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.

PubMed: 27060135
DOI: 10.1093/nar/gkw218

Experimental method

X-RAY DIFFRACTION (3.012 Å)