PXD071378 is an
original dataset announced via ProteomeXchange.
Dataset Summary
| Title | Induced ubiquitination of the partially disordered Estrogen Receptor alpha protein via a 14-3-3-directed molecular glue-based PROTAC design |
| Description | Proteins lacking defined ligandable pockets remain challenging drug targets. Here, we develop a molecular glue-based PROTAC (MGPROTACs) approach that chemically conjugates a molecular glue stabilizer to a VHL-recruiting ligand to capture and ubiquitinate the 14-3-3/Estrogen Receptor α (ERα) complex. Our designed MGPROTACs engage a composite interface between 14-3-3 and the disordered F-domain of ERα, promoting cooperative complex formation and target ubiquitination. Biophysical characterization revealed distinct linker-dependent cooperativities across the MGPROTAC series, which influenced both cellular permeability and ubiquitination efficiency. Cryo-EM of the most cooperative MGPROTAC uncovers de novo VHL–14-3-3ζ contacts, while molecular dynamics simulations rationalize the stabilizing interactions underlying cooperativity. Strikingly, finetuning linker design enables selective ubiquitination of distinct complex subunits. These findings establish a structural and mechanistic framework for integrating molecular glue and PROTAC principles, expanding the scope of drug discovery to previously intractable protein complexes |
| HostingRepository | PRIDE |
| AnnounceDate | 2026-07-07 |
| AnnouncementXML | Submission_2026-07-07_03:10:39.742.xml |
| DigitalObjectIdentifier | |
| ReviewLevel | Peer-reviewed dataset |
| DatasetOrigin | Original dataset |
| RepositorySupport | Unsupported dataset by repository |
| PrimarySubmitter | Gajanan Sathe |
| SpeciesList | scientific name: Homo sapiens (Human); NCBI TaxID: NEWT:9606; |
| ModificationList | ubiquitination signature dipeptidyl lysine |
| Instrument | Orbitrap Ascend |
Dataset History
| Revision | Datetime | Status | ChangeLog Entry |
|---|
| 0 | 2025-11-28 13:26:07 | ID requested | |
| ⏵ 1 | 2026-07-07 03:10:40 | announced | |
Publication List
Keyword List
| submitter keyword: Estrogen Receptor α (ERα) ,PROTAC,TPD,14-3-3 |
Contact List
| Peter Cossar |
|---|
| contact affiliation | Principal Investigator Centre for Targeted Protein Degradation University of dundee |
| contact email | PCossar001@dundee.ac.uk |
| lab head | |
| Gajanan Sathe |
|---|
| contact affiliation | Centre for Targeted Protein Degradation (CeTPD)
University of Dundee |
| contact email | gsathe001@dundee.ac.uk |
| dataset submitter | |
Full Dataset Link List
Dataset FTP location
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| PRIDE project URI |
Repository Record List
[ + ]
[ - ]
- PRIDE
- PXD071378
- Label: PRIDE project
- Name: Induced ubiquitination of the partially disordered Estrogen Receptor alpha protein via a 14-3-3-directed molecular glue-based PROTAC design
