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PXD044126-1

PXD044126 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleDegron mimicry modulates selective substrate recruitment by CTLH E3 supramolecular assembly
DescriptionSelective protein degradation by the Ubiquitin Proteasome System (UPS) is largely regulated by multi-subunit E3 ligase complexes commonly utilizing interchangeable degron-receptors to target a plethora of different substrates. Here, we identified nicotinamide/nicotinacid-mononlucletide-adenylyltransferase 1 (NMNAT1) as a cognate substrate of CTLH E3 complex, and report structural, biochemical, and cell biology studies revealing a mechanism of a degron-selective receptor function of the inherent non-interchangeable CTLH supramolecular assembly subunit WDR26, tailored to avidly bind and target NMNAT1 hexamer. Importantly, WDR26 receptor is gated by a degron-mimicry of the N-terminus of the CTLH subunit YPEL5 that corrupts ubiquitin targeting of NMNAT1. Cellular YPEL5 depletion is sufficient to destabilize NMNAT1 and to attenuate cytotoxicity of the NMNAT1-activated anticancer drug Tiazofurin. Cumulatively, we propose a regulatory concept of degron selection and binding by the WDR26-CTLH supramolecular assembly, potentially applying to substrates other than NMNAT1.
HostingRepositoryPRIDE
AnnounceDate2024-05-16
AnnouncementXMLSubmission_2024-05-16_08:32:52.955.xml
DigitalObjectIdentifier
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterMario Oroshi
SpeciesList scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationListNo PTMs are included in the dataset
InstrumentOrbitrap Exploris 480
Dataset History
RevisionDatetimeStatusChangeLog Entry
02023-07-27 00:00:53ID requested
12024-05-16 08:32:53announced
Publication List
Dataset with its publication pending
Keyword List
submitter keyword: Proteomics
Contact List
Matthias Mann
contact affiliationUnknown
contact emailmmann@biochem.mpg.de
lab head
Mario Oroshi
contact affiliationProteomics
contact emailoroshi@biochem.mpg.de
dataset submitter
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Dataset FTP location
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