PXD049330 is an
original dataset announced via ProteomeXchange.
Dataset Summary
Title | Alkylamine-tethered molecules recruit FBXO22 for targeted protein degradation |
Description | Targeted Protein Degradation (TPD) utilizes small molecules to direct proteins towards E3 ubiquitin ligases for degradation, but is limited by the small number of ligases accessible for this approach. We introduce SP3N, a novel degrader targeting FKBP12, designed with a simple structure that integrates a FKBP12 ligand with a degradation-inducing alkylamine tail. Through comprehensive target identification, we show that SP3N acts as a prodrug, converting its alkylamine to an active aldehyde that engages the SCF FBXO22 ligase for FKBP12's degradation via covalent attachment to FBXO22's Cys326, essential for the degradation process. This mechanism, also applicable to NSD2 and XIAP degraders, presents a new, broadly applicable TPD method involving alkylamine-based tethering and covalent modification of FBXO22. |
HostingRepository | PRIDE |
AnnounceDate | 2024-10-22 |
AnnouncementXML | Submission_2024-10-22_06:47:21.974.xml |
DigitalObjectIdentifier | |
ReviewLevel | Peer-reviewed dataset |
DatasetOrigin | Original dataset |
RepositorySupport | Unsupported dataset by repository |
PrimarySubmitter | Kevin Dong |
SpeciesList | scientific name: Homo sapiens (Human); NCBI TaxID: 9606; |
ModificationList | iodoacetamide derivatized residue |
Instrument | Orbitrap Fusion Lumos |
Dataset History
Revision | Datetime | Status | ChangeLog Entry |
0 | 2024-02-12 05:54:24 | ID requested | |
1 | 2024-06-24 06:26:07 | announced | |
⏵ 2 | 2024-10-22 06:47:22 | announced | 2024-10-22: Updated project metadata. |
Publication List
Dataset with its publication pending |
Keyword List
submitter keyword: whole proteome,PROTAC, degradation |
Contact List
Georg E. Winter |
contact affiliation | CeMM Principal Investigator |
contact email | GWinter@cemm.oeaw.ac.at |
lab head | |
Kevin Dong |
contact affiliation | Harvard Medical School |
contact email | kevindong@g.harvard.edu |
dataset submitter | |
Full Dataset Link List
Dataset FTP location
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PRIDE project URI |
Repository Record List
[ + ]
[ - ]
- PRIDE
- PXD049330
- Label: PRIDE project
- Name: Alkylamine-tethered molecules recruit FBXO22 for targeted protein degradation