PXD081566

PXD081566 is an original dataset announced via ProteomeXchange.

Title	Photocatalytic zero-length proximity crosslinking reconstructs dynamic protein degradation networks in living cells
Description	Protein interaction networks are dynamically remodeled during signaling and proteostasis, but many transient, low-stoichiometry, or degradation-coupled contacts are lost during affinity purification and difficult to distinguish from proximity-labeling backgrounds. Here, we introduce photocatalytic zero-length proximity crosslinking (PZPC), a genetically encoded, blue-light-controlled strategy that covalently captures protein-of-interest-containing covalent complexes in living cells. We further develop LinkMasser, a blind-search crosslinking mass spectrometry algorithm that identifies unknown crosslink-associated mass offsets, revealing an oxidative Lys–His zero-length coupling signature underlying PZPC-mediated crosslinking. Using the ubiquitin-independent degradation factor midnolin as a benchmark system, PZPC recovered inducible transcription factors and short-lived regulatory proteins largely missed by conventional AP–MS, leading to the identification of five novel midnolin substrates. We next applied PZPC to 63 human F-box proteins, generating a family-wide proximity atlas of 554 candidate interactors and functionally validating 81 candidate substrates from 257 tested proteins. By coupling this atlas to an antiviral signaling screen, we identified FBXO44 as a positive regulator of the RIG-I–MAVS–IFN pathway and degraded ADAR1, EIF3B, and TUFM as FBXO44-regulated negative modulators of antiviral signaling. These results establish PZPC as a scalable framework for resolving dynamic protein networks and uncovering E3-regulated signaling circuits in living cells.
HostingRepository	iProX
AnnounceDate	2026-07-23
AnnouncementXML	Submission_2026-07-23_20:02:31.885.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Xinyu Zhang
SpeciesList	scientific name: Homo sapiens; NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	Q Exactive Plus

Revision	Datetime	Status	ChangeLog Entry
0	2026-07-23 19:58:47	ID requested
⏵ 1	2026-07-23 20:02:32	announced

Dataset with its publication pending

submitter keyword: protein-protein interaction, proteomics, proximity crosslinking, F-box proteins, protein degradation

Gang Li
contact affiliation	Shenzhen Bay Laboratory
contact email	ligang@szbl.ac.cn
lab head
Xinyu Zhang
contact affiliation	Shenzhen Medical Academy of Research and Translation
contact email	15386853933@163.com
dataset submitter

iProX dataset URI