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PXD080648

PXD080648 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleIdentification of the NLRP3 inflammasome interactome
DescriptionNLRP3 is activated by many stimuli and its dysfunction is involved in various autoinflammatory diseases. NLRP3 aggregates preceding the release of its autoinhibitory conformation where scaffold proteins mediating aggregation are proposed. How NLRP3 releases auto-repression remains elusive. Here, we report that activating molecule in Beclin1-regulated autophagy protein 1 (AMBRA1) binds NLRP3 to scaffold and allosterically activate NLRP3. AMBRA1 engages NLRP3’s transition LRR and HD2 subdomains via its β-propeller to destabilize the closed inactive NLRP3 conformation, facilitating ATP binding and transition to the active state, which is similar to Apaf1-scaffolded apoptosome assembly. AMBRA1 deficiency in cells and in mice impairs NLRP3 activation and inflammatory responses in mouse models. Blocking AMBRA1-NLRP3 interaction by nanobodies inhibits NLRP3 activation, underscoring the therapeutic potential of targeting this interaction. This study implies a conserved activating mechanism shared by both apoptotic and pyroptotic cell death and β-propeller-containing partners like AMBRA1 are required for the activation of NLRPs.
HostingRepositoryiProX
AnnounceDate2026-07-06
AnnouncementXMLSubmission_2026-07-07_00:01:37.275.xml
DigitalObjectIdentifier
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterMinghui Pan
SpeciesList scientific name: Homo sapiens; NCBI TaxID: 9606;
ModificationListNo PTMs are included in the dataset
InstrumentOrbitrap Fusion Lumos
Dataset History
RevisionDatetimeStatusChangeLog Entry
02026-07-07 00:00:54ID requested
12026-07-07 00:01:37announced
Publication List
Dataset with its publication pending
Keyword List
submitter keyword: NLRP3 inflammasome, protein‑protein interaction, THP‑1 cells
Contact List
Zhengfan Jiang
contact affiliationPeking University
contact emailjiangzf@pku.edu.cn
lab head
Minghui Pan
contact affiliationPeking University
contact email1196256385@qq.com
dataset submitter
Full Dataset Link List
iProX dataset URI