PXD078039-1

PXD078039 is an original dataset announced via ProteomeXchange.

Title	An Integrated Platform for In vivo Imaging, Compositional Profiling, and Interactome Mapping of the Aggregated Proteome in Live Cells
Description	Protein misfolding and aberrant aggregation are fundamental to neurodegenerative diseases, but studying these dynamic, heterogeneous complexes within their native cellular environment remains a major challenge. We present an integrated chemical proteomics platform that enables concurrent in situ imaging, compositional profiling, and interactome mapping of the aggregated proteome in live cells. The platform combines a novel aggregate-targeting photosensitizer probe (D6) for photocatalytic proximity labeling with a biocompatible, mass-spectrometry-cleavable crosslinker, trehalose disuccinimidyl ester (TDS). This allows for the covalent capture of transient protein conformations and interactions within aggregates prior to their isolation and analysis. Applying this method to a cellular model of proteostasis stress, we identified 1,165 enriched aggregate constituents and mapped 739 protein-protein interactions (67.8% novel), revealing a densely interconnected network centered on the chaperone HSPA1B (HSP70). Functional validation demonstrated that pharmacological activation of HSP70, the central hub of this network, directly promotes the disassembly and clearance of mutant huntingtin aggregates. Our work provides a comprehensive spatial and functional atlas of the aggregated proteome and establishes a generalizable platform for uncovering the mechanisms and therapeutic targets of protein conformational diseases.
HostingRepository	iProX
AnnounceDate	2026-04-30
AnnouncementXML	Submission_2026-05-06_01:05:06.214.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Nan Zhao
SpeciesList	scientific name: Homo sapiens; NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	Orbitrap Exploris 480; Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2026-05-06 01:04:46	ID requested
⏵ 1	2026-05-06 01:05:07	announced

Dataset with its publication pending

submitter keyword: in situ fluorescence imaging, photocatalytic proximity labeling, in vivo crosslinking, aggregated proteome, chaperone proteins

Lihua Zhang
contact affiliation	Dalian Institute of Chemical Physics
contact email	lihuazhang@dicp.ac.cn
lab head
Nan Zhao
contact affiliation	Dalian Institute of Chemical Physics
contact email	zhaonan@dicp.ac.cn
dataset submitter

iProX dataset URI