PXD049330-2

PXD049330 is an original dataset announced via ProteomeXchange.

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

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.

Dataset with its publication pending

submitter keyword: whole proteome,PROTAC, degradation

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

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PRIDE project URI

• PRIDE
  1. PXD049330
     1. Label: PRIDE project
     2. Name: Alkylamine-tethered molecules recruit FBXO22 for targeted protein degradation