8TX8

Crystal Structure of RBBP4 bound to ZNF512B peptide

8TX8 の概要

• エントリーDOI: 10.2210/pdb8tx8/pdb
• 分子名称: Histone-binding protein RBBP4, Zinc finger protein 512B, FORMIC ACID, ... (7 entities in total)
• 機能のキーワード: nurd, chromatin compaction, zinc finger, transcription
• 由来する生物種: Homo sapiens (human); 詳細
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 104100.75

構造登録者

Deshpande, C.N.,Mackay, J.P. (登録日: 2023-08-22, 公開日: 2024-11-06, 最終更新日: 2024-12-11)

主引用文献

Wunderlich, T.M.,Deshpande, C.,Paasche, L.W.,Friedrich, T.,Diegmuller, F.,Haddad, E.,Kreienbaum, C.,Naseer, H.,Stebel, S.E.,Daus, N.,Leers, J.,Lan, J.,Trinh, V.T.,Vazquez, O.,Butter, F.,Bartkuhn, M.,Mackay, J.P.,Hake, S.B.
ZNF512B binds RBBP4 via a variant NuRD interaction motif and aggregates chromatin in a NuRD complex-independent manner.
Nucleic Acids Res., 52:12831-12849, 2024

PubMed Abstract: The evolutionarily conserved histone variant H2A.Z plays a crucial role in various DNA-based processes, but the mechanisms underlying its activity are not completely understood. Recently, we identified the zinc finger (ZF) protein ZNF512B as a protein associated with H2A.Z, HMG20A and PWWP2A. Here, we report that high levels of ZNF512B expression lead to nuclear protein and chromatin aggregation foci that form in a manner that is dependent on the ZF domains of ZNF512B. Notably, we demonstrate ZNF512B binding to the nucleosome remodeling and deacetylase (NuRD) complex. We discover a conserved amino acid sequence within ZNF512B that resembles the NuRD-interaction motif (NIM) previously identified in FOG-1 and other transcriptional regulators. By solving the crystal structure of this motif bound to the NuRD component RBBP4 and by applying several biochemical and biophysical assays, we demonstrate that this internal NIM is both necessary and sufficient for robust and high-affinity NuRD binding. Transcriptome analyses and reporter assays identify ZNF512B as a repressor of gene expression that can act in both NuRD-dependent and -independent ways. Our study might have implications for diseases in which ZNF512B expression is deregulated, such as cancer and neurodegenerative diseases, and hints at the existence of more proteins as potential NuRD interactors.

PubMed: 39460621
DOI: 10.1093/nar/gkae926

実験手法

X-RAY DIFFRACTION (2.2 Å)