Nucleic Acids Research, 6 August, 2025, DOI：https://doi.org/10.1093/nar/gkaf735

AlphaFold-guided structural analyses of nucleosome binding proteins

Xin Yang, Haoqiang Zhu, Liuxin Shi, Tingrui Song, Weibin Gong, Shunmin He, Shan Shan, Chunfu Xu, Zheng Zhou

Abstract

The nucleosome, as the fundamental unit of chromatin, interacts with a diverse range of proteins, crucially regulating gene expression. In this study, we introduce an AlphaFold-based algorithm designed to analyze nucleosome-binding proteins from a dataset of over 7600 human nuclear proteins. Using proteins that interact with the nucleosome acidic patch as a benchmark, our screening achieves a successful prediction rate of 77% (23 out of 30 proteins). This predictive approach has led to the identification of ARID4A and ARID4B as novel nucleosome-binding proteins. Additionally, this analytical method was used to study RING-family ubiquitin E3 ligase RNF168, demonstrating that RNF168 dimerization enhances its binding to the nucleosome, a finding confirmed by cryogenic-electron microscopy structural analysis. Our findings offer a rapid and effective method for the discovery and characterization of nucleosome-binding proteins and emphasize the significant role of ubiquitin E3 ligase dimerization in epigenetic regulation.

Article link：https://academic.oup.com/nar/article/53/14/gkaf735/8223175