Details

Autor(en) / Beteiligte

• Zhang, Zhi-Min
• Rothbart, Scott B.
• Allison, David F.
• Cai, Qian
• Harrison, Joseph S.
• Li, Lin
• Wang, Yinsheng
• Strahl, Brian D.
• Wang, Gang Greg
• Song, Jikui

Titel

An Allosteric Interaction Links USP7 to Deubiquitination and Chromatin Targeting of UHRF1

Ist Teil von

• Cell reports (Cambridge), 2015-09, Vol.12 (9), p.1400-1406

Ort / Verlag

United States: Elsevier Inc

Erscheinungsjahr

2015

Link zum Volltext

Quelle

MEDLINE

Beschreibungen/Notizen

• 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. [Display omitted] •USP7 ubiquitin-like domains bind to the UHRF1 polybasic region•USP7 interaction promotes USP7-mediated deubiquitination of UHRF1•USP7 allosterically regulates the conformational states of UHRF1•USP7 interaction affects the chromatin association of UHRF1 Zhang et al. report the crystal structure of USP7 ubiquitin-like domains in complex with the UHRF1 polybasic region. Structural analysis, combined with biochemical and cellular analysis, reveals that the USP7 interaction influences both ubiquitination and chromatin association of UHRF1.