SNAP annotations: PDB entry 9hju

PDB-id

9hju; DSSR-derived features in text and JSON formats; DNAproDB

Class

structural protein

Method

cryo-EM (3.16 Å)

Summary

Structure of 2x zincore (sephs1:qrich1) binding to zfp91 on DNA

Reference

Bianchi D, Borza R, De Zan E, Huelsz-Prince G, Gregoricchio S, Dekker M, Fish A, Mazouzi A, Kroese LJ, Linder S, Hernandez-Quiles M, Vermeulen M, Celie PHN, Krimpenfort P, Song JY, Zwart W, Wessels L, Nijman SMB, Perrakis A, Brummelkamp TR (2025): "Zincore, an atypical coregulator, binds zinc finger transcription factors to control gene expression." Science, 389, eadv2861. doi: 10.1126/science.adv2861.

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.