PXD068622

PXD068622 is an original dataset announced via ProteomeXchange.

Title	Dual Proximity Labeling Strategy Identifies TrxR1 as a Cuproprotein that Regulates Apoptosis via Caspase-3 S-Nitrosylation
Description	Copper (Cu) performs essential structural and functional roles in all aerobic organisms, but identifying natural cuproproteins through traditional affinity methods is hindered by the variety of copper ligand combinations and binding locations in proteins. Here, using ATOX1 as a bait, fused with the APEX2 or TurboID proximity labeling enzymes, with quantitative proteomics in cancer and normal cells (H1299 and HEK293T), we predicted 682 highly enriched candidate Cu-binding proteins. Among them, we functionally validated the novel cuproprotein, thioredoxin reductase 1 (TrxR1). Through cryo-electron microscopy (cryo-EM), we resolved three copper-binding sites across its N- and C-terminal redox centers. Functional assays demonstrated that copper inhibits TrxR1 reductase activity and impairs the denitrosylation function of its substrate, thioredoxin 1 (Trx1), consequently inhibiting caspase-3 cleavage and apoptosis. Beyond expanding the scope of annotated cuproproteins, this study provides a versatile strategy for cuproprotein discovery and defines the copper functions in modulating apoptosis through the TrxR1/Trx1 regulatory module.
HostingRepository	iProX
AnnounceDate	2025-09-22
AnnouncementXML	Submission_2025-09-21_23:34:19.605.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Zhengcunxiao Li
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	2025-09-21 23:32:25	ID requested
⏵ 1	2025-09-21 23:34:19	announced

Dataset with its publication pending

submitter keyword: ATOX1, cuproproteins, proximity labeling

Jing Wang
contact affiliation	Peking University
contact email	wangjingsioc@pku.edu.cn
lab head
Zhengcunxiao Li
contact affiliation	Peking University
contact email	1054524763@qq.com
dataset submitter

iProX dataset URI