5C6D

Crystal structure of USP7 in complex with UHRF1

Summary for 5C6D

• Entry DOI: 10.2210/pdb5c6d/pdb
• Descriptor: Ubiquitin carboxyl-terminal hydrolase 7, E3 ubiquitin-protein ligase UHRF1 (3 entities in total)
• Functional Keywords: usp7, uhrf1, hydrolase-ligase complex, hydrolase/ligase
• Biological source: Homo sapiens (Human); More
• Cellular location: Nucleus : Q93009 Q96T88
• Total number of polymer chains: 4
• Total formula weight: 81486.19

Authors

Zhang, Z.-M.,Song, J. (deposition date: 2015-06-22, release date: 2015-09-09, Last modification date: 2023-09-27)

Primary citation

Zhang, Z.M.,Rothbart, S.B.,Allison, D.F.,Cai, Q.,Harrison, J.S.,Li, L.,Wang, Y.,Strahl, B.D.,Wang, G.G.,Song, J.
An Allosteric Interaction Links USP7 to Deubiquitination and Chromatin Targeting of UHRF1.
Cell Rep, 12:1400-1406, 2015

PubMed Abstract: The protein stability and chromatin functions of UHRF1 (ubiquitin-like, containing PHD and RING finger domains, 1) are regulated in a cell-cycle-dependent manner. We report a structural characterization of the complex between UHRF1 and the deubiquitinase USP7. The first two UBL domains of USP7 bind to the polybasic region (PBR) of UHRF1, and this interaction is required for the USP7-mediated deubiquitination of UHRF1. Importantly, we find that the USP7-binding site of the UHRF1 PBR overlaps with the region engaging in an intramolecular interaction with the N-terminal tandem Tudor domain (TTD). We show that the USP7-UHRF1 interaction perturbs the TTD-PBR interaction of UHRF1, thereby shifting the conformation of UHRF1 from a TTD-"occluded" state to a state open for multivalent histone binding. Consistently, introduction of a USP7-interaction-defective mutation to UHRF1 significantly reduces its chromatin association. Together, these results link USP7 interaction to the dynamic deubiquitination and chromatin association of UHRF1.

PubMed: 26299963
DOI: 10.1016/j.celrep.2015.07.046

Experimental method

X-RAY DIFFRACTION (2.292 Å)