PXD053923

PXD053923 is an original dataset announced via ProteomeXchange.

Title	Distinct Perception Mechanisms of BACH1 Quaternary Structure Degrons by Two F-box Proteins under Oxidative Stress
Description	Ubiquitin-dependent proteolysis regulates diverse cellular functions with high substrate specificity. The precision of this regulatory mechanism hinges on the ability of ubiquitin E3 ligases to decode the targets’ degradation signals, i.e. degrons, which canonically present as short linear motifs. Here we show that BACH1, a transcription repressor of antioxidant response genes, features two distinct unconventional degrons encrypted in the quaternary structure of its homodimeric BTB domain. These two degrons are both functionalized by oxidative stress and are deciphered by two complementary E3s. FBXO22 recognizes a degron constructed by the BACH1 BTB domain dimer interface, which is unmasked from the co-repressor NCOR1 after BACH1 is released from chromatin by excessive heme. When this degron is impaired by oxidation, a second BACH1 degron embodied by the resulting BTB dimer with compromised integrity is probed by a pair of FBXL17 that remodels the two BTB protomers into E3-bound monomers for ubiquitination. Our findings reveal the remarkable multidimensionality of protein degradation signals underpinning substrate selectivity and functional versatility of ubiquitin-dependent proteolysis.
HostingRepository	PRIDE
AnnounceDate	2025-12-29
AnnouncementXML	Submission_2025-12-28_16:15:37.034.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Ellie James
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: NEWT:9606;
ModificationList	dihydroxylated residue; S-nitrosyl-L-cysteine; monohydroxylated residue
Instrument	Orbitrap Fusion

Revision	Datetime	Status	ChangeLog Entry
0	2024-07-12 12:13:51	ID requested
⏵ 1	2025-12-28 16:15:38	announced

10.1016/j.cell.2024.10.012;

ProteomeXchange project tag: Hydrogen Deuterium Exchange (HDX-MS)

submitter keyword: Oxidative Stress, Ubiquitination, Protein Degradation, Ubiquitin Ligase,BACH1, FBXL17, Transcription Repressor, FBXO22, BTB domain, SCF, Degron, Cryo-EM, HDX-MS

Miklos Guttman
contact affiliation	Medicinal Chemistry, School of Pharmacy, University of Washington, USA
contact email	mguttman@uw.edu
lab head
Ellie James
contact affiliation	University of Washington Medicinal Chemistry
contact email	elliej3@uw.edu
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD053923
     1. Label: PRIDE project
     2. Name: Distinct Perception Mechanisms of BACH1 Quaternary Structure Degrons by Two F-box Proteins under Oxidative Stress