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-Structure paper
Title | MORC2 is a phosphorylation-dependent DNA compaction machine. |
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Journal, issue, pages | Nat Commun, Vol. 16, Issue 1, Page 5606, Year 2025 |
Publish date | Jul 1, 2025 |
![]() | Winnie Tan / Jeongveen Park / Hariprasad Venugopal / Jieqiong Lou / Prabavi Shayana Dias / Pedro L Baldoni / Kyoung-Wook Moon / Toby A Dite / Christine R Keenan / Alexandra D Gurzau / Joonyoung Lee / Timothy M Johanson / Andrew Leis / Jumana Yousef / Vineet Vaibhav / Laura F Dagley / Ching-Seng Ang / Laura D Corso / Chen Davidovich / Stephin J Vervoort / Gordon K Smyth / Marnie E Blewitt / Rhys S Allan / Elizabeth Hinde / Sheena D'Arcy / Je-Kyung Ryu / Shabih Shakeel / ![]() ![]() ![]() |
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 ...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. |
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Methods | EM (single particle) |
Resolution | 1.95 - 3.24 Å |
Structure data | EMDB-45474, PDB-9cdf: EMDB-45475, PDB-9cdg: EMDB-45476, PDB-9cdh: EMDB-45477, PDB-9cdi: EMDB-45478, PDB-9cdj: |
Chemicals | ![]() ChemComp-ZN: ![]() ChemComp-ANP: ![]() ChemComp-MG: ![]() ChemComp-ATP: |
Source |
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![]() | DNA BINDING PROTEIN / Chromatin remodeller / complex / ATPase / ATPase dead / DNA compaction / AMP-PNP / DNA |