⮝ Full datasets listing
PXD071690
PXD071690 is an original dataset announced via ProteomeXchange.
Dataset Summary
| Title | The molecular basis for nuclear pore destruction by a proximity-inducing molecular glue |
| Description | Molecular glues that induce new protein interactions can be potent therapeutics. We and others recently discovered that the small molecule PRLX-93936 (PRLX), which was originally developed as an erastin derivative with antitumor activity, is a molecular glue that alters the substrate specificity of the TRIM21 ubiquitin ligase. PRLX causes TRIM21 to bind the nuclear pore protein NUP98, triggering nuclear pore complex (NPC) degradation. We present here the structural and biochemical basis of NUP98 recognition, finding that ternary complex assembly depends on creation of a composite TRIM21-small molecule surface competent for NUP98 binding. A scarcity of direct small molecule-NUP98 contacts likely explains how multiple structurally diverse TRIM21 ligands can induce NPC degradation. We also report the discovery of an enhanced molecular glue, MAN-021, and describe its structure. Our findings provide a basis for rational development of next-generation small molecules with enhanced or differentiated activities. This submission contains the global proteome profiling to identify downregulated proteins upon MAN021 treatment in PANC1 cells. |
| HostingRepository | MassIVE |
| AnnounceDate | 2026-05-27 |
| AnnouncementXML | Submission_2026-05-27_13:21:43.597.xml |
| DigitalObjectIdentifier | |
| ReviewLevel | Peer-reviewed dataset |
| DatasetOrigin | Original dataset |
| RepositorySupport | Unsupported dataset by repository |
| PrimarySubmitter | Brendan Dwyer |
| SpeciesList | scientific name: Homo sapiens; common name: human; NCBI TaxID: 9606; |
| ModificationList | Carbamidomethyl |
| Instrument | timsTOF HT |
Dataset History
| Revision | Datetime | Status | ChangeLog Entry |
|---|---|---|---|
| 0 | 2025-12-07 18:23:20 | ID requested | |
| ⏵ 1 | 2026-05-27 13:21:44 | announced |
Publication List
| . The molecular basis for nuclear pore destruction by a proximity-inducing molecular glue. https://doi.org/10.1016/j.chembiol.2026.04.016. |
Keyword List
| submitter keyword: targeted protein degradation, nuclear pore complex, global proteome profiling, DatasetType:Proteomics |
Contact List
| Nathanael S. Gray | |
|---|---|
| contact affiliation | Stanford University |
| contact email | nsgray01@stanford.edu |
| lab head | |
| Brendan Dwyer | |
| contact affiliation | Stanford University |
| contact email | dwyermrbrendan@gmail.com |
| dataset submitter | |
Full Dataset Link List
| MassIVE dataset URI |
| Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://massive-ftp.ucsd.edu/v11/MSV000100139/ |
