PXD074330

PXD074330 is an original dataset announced via ProteomeXchange.

Title	Poly(GR) Drives Intra-Condensate Demixing and Pathological Aggregation of TDP-43
Description	TAR DNA-binding protein 43 (TDP-43) pathology and C9orf72 hexanucleotide repeat expansions are two major pathological features of amyotrophic lateral sclerosis and frontotemporal dementia (ALS/FTD). Growing evidence indicates that dipeptide repeat proteins produced from C9orf72 repeats, particularly glycine–arginine (poly(GR)), promote TDP-43 aggregation, but the underlying mechanism remains unclear. Here we show that poly(GR) enhances liquid–liquid phase separation (LLPS) of TDP-43 and induces phase demixing within the resulting condensates. Demixed condensates contain regions with high local TDP-43 concentration that progressively solidify and undergo conformational changes from dynamic assemblies into oligomeric and fibrillar species rich in β-sheet structure, which promote the formation of toxic TDP-43 aggregates in cellular assays. Together, these findings support a mechanism in which phase separation enables poly(GR) to promote pathological TDP-43 aggregation and highlight condensate demixing and conformational conversion, constituting a key pathway for TDP-43 aggregation and a potential target for therapeutic intervention.
HostingRepository	iProX
AnnounceDate	2026-02-11
AnnouncementXML	Submission_2026-02-10_23:39:24.967.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Yida Jiang
SpeciesList	scientific name: Homo sapiens; NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2026-02-10 23:38:48	ID requested
⏵ 1	2026-02-10 23:39:25	announced

Dataset with its publication pending

submitter keyword: TDP-43, photo-cross-link, SDA, BDG

Chun Tang
contact affiliation	Beijing National Laboratory for Molecular Sciences
contact email	tang_chun@pku.edu.cn
lab head
Yida Jiang
contact affiliation	Peking University
contact email	jiangyida@pku.edu.cn
dataset submitter

iProX dataset URI