PXD053379

PXD053379 is an original dataset announced via ProteomeXchange.

Title	MORC2 phosphorylation fine tunes its DNA compaction activity
Description	Variants in the poorly characterized oncoprotein, MORC2, a chromatin remodeling ATPase, lead to defects in epigenetic regulation and DNA damage response. MORC2 variants are associated with multiple cancers and neurological disorders. The C-terminal domain (CTD) of MORC2is often phosphorylated in DNA damage response and is known to induce cancer progression in in vivo and in vitro cancer models. However, it remains unclear how MORC2 CTD and its phosphorylation impacts its chromatin remodeling activity. Here, we report a molecular characterization of full-length, phosphorylated MORC2.We show thatMORC2 preferentially binds open chromatin, has multiple DNA binding sites with varying affinities and acts as a DNA sliding clamp. We identified a phosphate interacting motif within the CTD that dictates ATP hydrolysis and cooperative DNA binding. The DNA binding impacts several structural domains within the N-terminal ATPase region. We provide the first visual proof that MORC2 induces chromatin remodeling through ATP hydrolysis-dependent DNA compaction, where the speed of compaction is affected by its phosphorylation state. Together, our results reveal that phosphorylation of MORC2 CTD modulates its chromatin remodeling and could be an attractive target for therapeutics.
HostingRepository	PRIDE
AnnounceDate	2025-07-14
AnnouncementXML	Submission_2025-07-13_17:16:25.570.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Sheena D'Arcy
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	phosphorylated residue
Instrument	Synapt MS

Revision	Datetime	Status	ChangeLog Entry
0	2024-06-24 20:31:32	ID requested
⏵ 1	2025-07-13 17:16:26	announced

Tan W, Park J, Venugopal H, Lou J, Dias PS, Baldoni PL, Moon KW, Dite TA, Keenan CR, Gurzau AD, Lee J, Johanson TM, Leis A, Yousef J, Vaibhav V, Dagley LF, Ang CS, Corso LD, Davidovich C, Vervoort SJ, Smyth GK, Blewitt ME, Allan RS, Hinde E, D'Arcy S, Ryu JK, Shakeel S, MORC2 is a phosphorylation-dependent DNA compaction machine. Nat Commun, 16(1):5606(2025) [pubmed]

10.1038/s41467-025-60751-z;

submitter keyword: ATPase, MORC2, Single molecule,Cryo-EM, Crosslinking MS, FLIM-FRET, HDX-MS, Epigenetics, FFS, Chromatin remodeling

Sheena D'Arcy
contact affiliation	Department of Chemistry and Biochemistry, The University of Texas at Dallas
contact email	Sheena.DArcy@utdallas.edu
lab head
Sheena D'Arcy
contact affiliation	The University of Texas at Dallas
contact email	sheena.darcy@utdallas.edu
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD053379
     1. Label: PRIDE project
     2. Name: MORC2 phosphorylation fine tunes its DNA compaction activity