9K2W

Cryo-EM structure of USP7:DNMT1 complex; closed conformation

9K2W の概要

• エントリーDOI: 10.2210/pdb9k2w/pdb
• EMDBエントリー: 61999
• 分子名称: Ubiquitin carboxyl-terminal hydrolase 7, DNA (cytosine-5)-methyltransferase 1, ZINC ION (3 entities in total)
• 機能のキーワード: dna methylation, deubiquitination, structural protein
• 由来する生物種: Homo sapiens (human); 詳細
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 272574.55

構造登録者

Nakamura, N.,Arita, K. (登録日: 2024-10-18, 公開日: 2025-06-25, 最終更新日: 2026-01-14)

主引用文献

Nakamura, N.,Yoshimi, S.,Kikuchi, A.,Onoda, H.,Kori, S.,Nakanishi, M.,Nishiyama, A.,Arita, K.
Structures of USP7 in active and inactive states bound to DNMT1 revealed by cryo-EM.
Structure, 33:1510-1518.e5, 2025

PubMed Abstract: The ubiquitin signal generated by UHRF1 is essential for DNA methylation maintenance by recruiting DNA methyltransferase 1 (DNMT1) to hemimethylated DNA through strong binding of its replication foci targeting sequence (RFTS) domain to ubiquitinated histone H3. The ubiquitin-specific protease 7 (USP7) forms a complex with DNMT1 and removes ubiquitin from H3. However, it remains unknown how USP7 deubiquitinates ubiquitinated H3 upon strong binding of the DNMT1 RFTS domain. Here, we show the activation mechanism of USP7 by combining biochemical and structural studies. USP7 is inactive toward ubiquitinated H3 in complex with the RFTS domain. However, when complexed with DNMT1, USP7 efficiently deubiquitinates ubiquitinated H3. Cryogenic electron microscopy (cryo-EM) single particle analysis revealed that USP7 bound to DNMT1 undergoes an open (inactive) and closed (active) conformational transition. Our findings provide mechanistic insights into the activation of USP7 upon binding to DNMT1 and contribute to a better understanding of the deubiquitination process in DNA methylation maintenance.

PubMed: 40645181
DOI: 10.1016/j.str.2025.06.005

実験手法

ELECTRON MICROSCOPY (3.54 Å)