9V33

Calypso/Asx/NCP-ub complex

Summary for 9V33

• Entry DOI: 10.2210/pdb9v33/pdb
• EMDB information: 64748
• Descriptor: Histone H3, Histone H4, Histone H2A, ... (9 entities in total)
• Functional Keywords: pr-dub, calypso, polycomb, transcription/dna, transcription-dna complex
• Biological source: Xenopus laevis (African clawed frog); More
• Total number of polymer chains: 15
• Total formula weight: 396370.14

Authors

Wang, C.,He, J. (deposition date: 2025-05-21, release date: 2026-03-18)

Primary citation

Wang, C.,Sun, F.,Zhao, H.,Zhang, N.,Guan, J.,Zhou, Y.,Shuai, W.,Zheng, H.,He, J.
Structural basis of nucleosome deubiquitination by the bidentate Calypso/Asx complex.
Iscience, 29:114958-114958, 2026

PubMed Abstract: 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 homolog Calypso/Asx forms a bidentate dimer (Calypso: Asx) 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 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.

PubMed: 41782825
DOI: 10.1016/j.isci.2026.114958

Experimental method

ELECTRON MICROSCOPY (5.9 Å)