PXD044126-1

PXD044126 is an original dataset announced via ProteomeXchange.

Title	Degron mimicry modulates selective substrate recruitment by CTLH E3 supramolecular assembly
Description	Selective 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.
HostingRepository	PRIDE
AnnounceDate	2024-05-16
AnnouncementXML	Submission_2024-05-16_08:32:52.955.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Mario Oroshi
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	Orbitrap Exploris 480

Revision	Datetime	Status	ChangeLog Entry
0	2023-07-27 00:00:53	ID requested
⏵ 1	2024-05-16 08:32:53	announced

Dataset with its publication pending

submitter keyword: Proteomics

Matthias Mann
contact affiliation	Unknown
contact email	mmann@biochem.mpg.de
lab head
Mario Oroshi
contact affiliation	Proteomics
contact email	oroshi@biochem.mpg.de
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD044126
     1. Label: PRIDE project
     2. Name: Degron mimicry modulates selective substrate recruitment by CTLH E3 supramolecular assembly