PXD079555-1

PXD079555 is an original dataset announced via ProteomeXchange.

Title	Integrated Optoproteomics and AP-MS Reveals interactome Remodeling Upon NLRP3 Inflammasome Activation
Description	NOD-like receptor family pyrin domain-containing 3 (NLRP3) is a critical intracellular danger sensor that forms inflammasome complexes to drive inflammatory caspase activation; however, the components and dynamic organization of the NLRP3 inflammasome remain incompletely defined. Here, we systematically characterized stimulus-dependent perturbations of the NLRP3 inflammasome interaction landscape by generating antibody-based endogenous immunoprecipitation-mass spectrometry (IP-MS) datasets for both NLRP3 and the adaptor protein apoptosis-associated speck-like protein containing a CARD (ASC) in bone marrow-derived macrophages (BMDMs). Across these conditions, we identified 1,541 inflammasome-associated protein interactions (1,048 non-redundant), enabling quantitative comparison of interaction dynamics across first- and second-signal activation states. Differential interaction scoring revealed networks selectively enriched during inflammasome priming and activation. Integration of these interaction datasets with microscopy-guided photo-labelling (optoproteomics) of ASC specks identified inner membrane mitochondrial protein (IMMT) as a previously unrecognized component of the NLRP3 inflammasome that associates with both NLRP3 and ASC upon activation. Functional analyses demonstrated that Immt knockdown enhanced caspase-1 and gasdermin D cleavage, IL-1β secretion, lactate dehydrogenase (LDH) release, and ASC oligomerization in response to NLRP3 agonists, establishing IMMT as a negative regulator of inflammasome activation. Together, this study provides a comprehensive and stimulus-resolved proteomic map of NLRP3 and ASC interaction networks in macrophages and reveals IMMT as a regulatory factor in NLRP3 inflammasome assembly and signaling.
HostingRepository	iProX
AnnounceDate	2026-06-11
AnnouncementXML	Submission_2026-06-10_20:38:37.690.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Yuchen Liu
SpeciesList	scientific name: Mus musculus; NCBI TaxID: 10090;
ModificationList	No PTMs are included in the dataset
Instrument	timsTOF Pro; Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2026-06-10 20:37:41	ID requested
⏵ 1	2026-06-10 20:38:38	announced

Dataset with its publication pending

submitter keyword: ASC speck, Optoproteomics , AP-MS, stimulation

Jian Wang
contact affiliation	National Center for Protein Sciences (Beijing)
contact email	wangj.bio@foxmail.com
lab head
Yuchen Liu
contact affiliation	National Center for Protein Sciences (Beijing)
contact email	liuyuchen@ncpsb.org.cn
dataset submitter

iProX dataset URI