2026-10-14T02:34:45Z https://www.scidb.cn/oai

10.57760/sciencedb.37309 2026-02-13T09:45:51Z

2026-02-13 Structural Basis of Nucleosome Deubiquitination by the Bidentate Calypso/Asx Complex doi:10.57760/sciencedb.37309 en The Polycomb Repressive Complex 1 (PRC1) and PR-DUB constitute a canonical pair of histone-modifying enzymes that deposit and remove monoubiquitinated H2A at lysine 119 (H2AK119ub1), serving as a model of dynamic epigenetic regulation. In humans, PR-DUB, composed of BAP1 and ASXL1, functions as a monomeric complex, while the Drosophila homolog Calypso/Asx forms a bidentate dimer (Calypso2: Asx2) with an unclear chromatin engagement mechanism. Here, we present its cryo-EM structure bound to a nucleosome, revealing the molecular basis of interaction. Surprisingly, only one Calypso/Asx unit engages the nucleosome in a conformation similar to human BAP1/ASXL1, while the second remains disengaged. Structural and biochemical analysis of the positively charged Calypso C-terminus suggests a “spreading” potential of the bidentate complex along chromatin, which was validated in vitro using nucleosome arrays. These findings support a model in which the bidentate Calypso/Asx complex enables processive deubiquitination along chromatin via alternating or cooperative engagement. "Ubiquitin C-terminal hydrolase; Polycomb repression; H2AK119ub1; Chromatin; PR-DUB" Chi Wang Fahui Sun Heyu Zhao Nan Zhang Jiali Guan Yuxing Zhou Wentong Shuai Hui Zheng* Jun He* PUBLIC https://creativecommons.org/licenses/by/4.0/ dataset http://www.doi.org/10.1016/j.isci.2026.114958 Science Data Bank