7D8A

Crystal Structure of H3(1-13)/PHF14-PZP fusion protein

7D8A の概要

• エントリーDOI: 10.2210/pdb7d8a/pdb
• 分子名称: PHD finger protein 14, Gene for histone H3 (germline gene), ZINC ION, ... (5 entities in total)
• 機能のキーワード: h3(1-13)/phf14-pzp, gene regulation
• 由来する生物種: Danio rerio (Zebrafish); 詳細
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 25410.24

構造登録者

Li, H.,Zheng, S. (登録日: 2020-10-07, 公開日: 2021-07-28, 最終更新日: 2023-11-29)

主引用文献

Zheng, S.,Bi, Y.,Chen, H.,Gong, B.,Jia, S.,Li, H.
Molecular basis for bipartite recognition of histone H3 by the PZP domain of PHF14.
Nucleic Acids Res., 49:8961-8973, 2021

PubMed Abstract: Histone recognition constitutes a key epigenetic mechanism in gene regulation and cell fate decision. PHF14 is a conserved multi-PHD finger protein that has been implicated in organ development, tissue homeostasis, and tumorigenesis. Here we show that PHF14 reads unmodified histone H3(1-34) through an integrated PHD1-ZnK-PHD2 cassette (PHF14PZP). Our binding, structural and HDX-MS analyses revealed a feature of bipartite recognition, in which PHF14PZP utilizes two distinct surfaces for concurrent yet separable engagement of segments H3-Nter (e.g. 1-15) and H3-middle (e.g. 14-34) of H3(1-34). Structural studies revealed a novel histone H3 binding mode by PHD1 of PHF14PZP, in which a PHF14-unique insertion loop but not the core β-strands of a PHD finger dominates H3K4 readout. Binding studies showed that H3-PHF14PZP engagement is sensitive to modifications occurring to H3 R2, T3, K4, R8 and K23 but not K9 and K27, suggesting multiple layers of modification switch. Collectively, our work calls attention to PHF14 as a 'ground' state (unmodified) H3(1-34) reader that can be negatively regulated by active marks, thus providing molecular insights into a repressive function of PHF14 and its derepression.

PubMed: 34365506
DOI: 10.1093/nar/gkab670

実験手法

X-RAY DIFFRACTION (2 Å)