9CDH

MORC2 PD mutant with DNA

9CDH の概要

• エントリーDOI: 10.2210/pdb9cdh/pdb
• 関連するPDBエントリー: 5OF9
• EMDBエントリー: 45476
• 分子名称: ATPase MORC2, ZINC ION, PHOSPHOAMINOPHOSPHONIC ACID-ADENYLATE ESTER, ... (4 entities in total)
• 機能のキーワード: atpase, chromatin remodeller, dna compaction, dna binding protein
• 由来する生物種: Homo sapiens (human)
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 237006.82

構造登録者

Tan, W.,Shakeel, S. (登録日: 2024-06-25, 公開日: 2025-07-09)

主引用文献

Tan, W.,Park, J.,Venugopal, H.,Lou, J.,Dias, P.S.,Baldoni, P.L.,Moon, K.W.,Dite, T.A.,Keenan, C.R.,Gurzau, A.D.,Lee, J.,Johanson, T.M.,Leis, A.,Yousef, J.,Vaibhav, V.,Dagley, L.F.,Ang, C.S.,Corso, L.D.,Davidovich, C.,Vervoort, S.J.,Smyth, G.K.,Blewitt, M.E.,Allan, R.S.,Hinde, E.,D'Arcy, S.,Ryu, J.K.,Shakeel, S.
MORC2 is a phosphorylation-dependent DNA compaction machine.
Nat Commun, 16:5606-5606, 2025

PubMed Abstract: The Microrchidia (MORC) family of chromatin-remodelling ATPases is pivotal in forming higher-order chromatin structures that suppress transcription. The exact mechanisms of MORC-induced chromatin remodelling have been elusive. Here, we report an in vitro reconstitution of full-length MORC2, the most commonly mutated MORC member, linked to various cancers and neurological disorders. MORC2 possesses multiple DNA-binding sites that undergo structural rearrangement upon DNA binding. MORC2 locks onto the DNA using its C-terminal domain (CTD) and acts as a clamp. A conserved phosphate-interacting motif within the CTD was found to regulate ATP hydrolysis and cooperative DNA binding. Importantly, MORC2 mediates chromatin remodelling via ATP hydrolysis-dependent DNA compaction in vitro, regulated by the phosphorylation state of its CTD. These findings position MORC2 CTD phosphorylation as a critical regulator of chromatin remodelling and a promising therapeutic target.

PubMed: 40593625
DOI: 10.1038/s41467-025-60751-z

実験手法

ELECTRON MICROSCOPY (1.95 Å)