9HJT

Structure of Zincore (SEPHS1:QRICH1) binding to ZFP91 on DNA

Summary for 9HJT

• Entry DOI: 10.2210/pdb9hjt/pdb
• Related: 9HJU
• EMDB information: 52226
• Descriptor: E3 ubiquitin-protein ligase ZFP91, Selenide, water dikinase 1, Transcriptional regulator QRICH1, ... (6 entities in total)
• Functional Keywords: zincore complex, transcriptional regulator complex, sephs1, selenide, water dikinase 1, selenophosphate synthetase 1, qrich1, zinc finger protein, zfp91, transcription factor, structural protein
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 7
• Total formula weight: 341875.72

Authors

Borza, R.,Perrakis, A. (deposition date: 2024-12-02, release date: 2025-07-09, Last modification date: 2025-07-16)

Primary citation

Bianchi, D.,Borza, R.,De Zan, E.,Huelsz-Prince, G.,Gregoricchio, S.,Dekker, M.,Fish, A.,Mazouzi, A.,Kroese, L.J.,Linder, S.,Hernandez-Quiles, M.,Vermeulen, M.,Celie, P.H.N.,Krimpenfort, P.,Song, J.Y.,Zwart, W.,Wessels, L.,Nijman, S.M.B.,Perrakis, A.,Brummelkamp, T.R.
Zincore, an atypical coregulator, binds zinc finger transcription factors to control gene expression.
Science, 389:eadv2861-eadv2861, 2025

PubMed Abstract: Zinc finger proteins (ZNFs) are the largest family of transcription factors, yet how they activate gene expression remains unclear. In this study, we identified Zincore, a protein complex consisting of QRICH1 and SEPHS1, as a ZNF-specific coregulator essential for embryonic development in mice and associated with developmental syndromes in humans. We also identified ZFP91 as a representative Zincore client, binding the conserved promoter motif CTTTAAR. Cryo-electron microscopy of a Zincore-ZFP91-DNA complex revealed a SEPHS1 arginine clamp to recognize the DNA-bound zinc finger domains. This mode of binding explains recognition of different ZNFs and stabilizes ZFP91 onto its cognate DNA motif. Thus, our study identified Zincore as a ZNF-specific coregulator essential for development, involving a distinctive mechanism that locks ZNFs onto DNA and regulates transcription.

PubMed: 40608935
DOI: 10.1126/science.adv2861

Experimental method

ELECTRON MICROSCOPY (3.26 Å)