PXD070446

PXD070446 is an original dataset announced via ProteomeXchange.

Title	Computational design of a versatile, zero-radius proximity labeling enzyme
Description	The ability to map cellular interactomes and organelle proteomes is foundational to a molecular understanding of cell biology. Proximity labeling (PL) provides a powerful strategy for such mapping, but existing enzymes and photocatalysts are limited by their reliance on biotin, spatial resolution, and/or in vivo compatibility. Here we report FlexID, an engineered promiscuous ligase that rapidly attaches diverse small-molecule probes to nearby cellular proteins through direct contact. We engineered FlexID using both sequence- and structure-trained computational models, combining their strengths for catalytic enhancement and structural stabilization. Biophysical analysis reveals that conformational changes in FlexID improve its ability to recognize diverse target proteins while preventing premature release of reactive intermediate. We demonstrate FlexID’s versatility through in vivo proximity labeling, comprehensive organelle proteome mapping, and high-throughput screening of molecular glues using fluorescence-based readout. Our work demonstrates that computational methods can be harnessed to create mechanistically distinct PL enzymes, and provides a flexible, high-resolution tool for mapping protein interactions and proteomes in living cells.
HostingRepository	iProX
AnnounceDate	2025-11-07
AnnouncementXML	Submission_2025-11-06_23:57:10.550.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Zijuan 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	2025-11-06 23:56:55	ID requested
⏵ 1	2025-11-06 23:57:11	announced

Dataset with its publication pending

submitter keyword: Proximity labeling, FlexID

Wei Qin
contact affiliation	Tsinghua University
contact email	weiqin@mail.tsinghua.edu.cn
lab head
Zijuan Zhang
contact affiliation	Tsinghua University
contact email	zj-zhang24@mails.tsinghua.edu.cn
dataset submitter

iProX dataset URI