9CDF
Structure of MORC2 PD mutant binding to AMP-PNP
Summary for 9CDF
| Entry DOI | 10.2210/pdb9cdf/pdb |
| Related | 5OF9 |
| EMDB information | 45474 |
| Descriptor | ATPase MORC2, ZINC ION, PHOSPHOAMINOPHOSPHONIC ACID-ADENYLATE ESTER, ... (4 entities in total) |
| Functional Keywords | chromatin remodeller, complex, dna binding protein, atpase |
| Biological source | Homo sapiens (human) |
| Total number of polymer chains | 2 |
| Total formula weight | 237006.82 |
| Authors | |
| Primary citation | 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 Cited by 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: 40593625DOI: 10.1038/s41467-025-60751-z PDB entries with the same primary citation |
| Experimental method | ELECTRON MICROSCOPY (2.39 Å) |
Structure validation
Download full validation report
