PXD053383-1

PXD053383 is an original dataset announced via ProteomeXchange.

Title	MORC2 phosphorylation fine tunes its DNA compaction activity
Description	Variants in the poorly characterised oncoprotein, MORC2, a chromatin remodelling ATPase, lead to defects in epigenetic regulation and DNA damage response. MORC2 variants are associated with multiple cancers and neurological disorders1,2. The C-terminal domain (CTD) of MORC2 is often phosphorylated in DNA damage response and is known to induce cancer progression in in vivo and in vitro cancer models3-5. However, it remains unclear how MORC2 CTD and its phosphorylation impacts its chromatin remodelling activity. Here, we report a molecular characterisation of full-length, phosphorylated MORC2. We show that MORC2 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 remodelling 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 remodelling and could be an attractive target for therapeutics.
HostingRepository	PRIDE
AnnounceDate	2025-05-05
AnnouncementXML	Submission_2025-05-05_15:55:51.616.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Laura Dagley
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	phosphorylated residue; monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2024-06-24 22:51:31	ID requested
⏵ 1	2025-05-05 15:55:51	announced

Dataset with its publication pending

submitter keyword: hydrogen deuterium exchange mass spectrometry, chromatin remodelling, crosslink mass spectrometry, ATPase, epigenetics, single molecule, FLIM-FRET, FFS,cryo-electron microscopy

Shabih Shakeel
contact affiliation	Laboratory Head The Walter and Eliza Hall Institute of Medical Research 1G Royal Parade Parkville Victoria 3052 Australia
contact email	shakeel.s@wehi.edu.au
lab head
Laura Dagley
contact affiliation	WEHI
contact email	dagley.l@wehi.edu.au
dataset submitter

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2025/05/PXD053383

PRIDE project URI

• PRIDE
  1. PXD053383
     1. Label: PRIDE project
     2. Name: MORC2 phosphorylation fine tunes its DNA compaction activity