PXD045212-1

PXD045212 is an original dataset announced via ProteomeXchange.

Title	HDX-MS analysis of IRGQ in the presence of GABARAP-L2 and LC3B
Description	The autophagy-lysosome system directs the degradation of a wide variety of cargo and is also involved in tumor progression. Here we show that immunity-related GTPase family Q protein (IRGQ) acts in the quality control of MHC-I molecules and directs misfolded MHC-I for lysosomal degradation through its binding to GABARAPL2 and LC3B. IRGQ specifically targets the non-conformational heavy chains of MHC-I, sorting them for degradation through the autophagy-lysosome system. In the absence of IRGQ, free MHC-I heavy chains accumulate in the cell and additionally get localized to the cell surface, thereby increasing interactions with mature MHC-I molecules and promoting immune response. Accordingly, mice suffering from hepatocellular carcinoma with reduced IRGQ levels display higher survival rates and bear more activated CD8+ T cells. Similarly, low IRGQ expression in human liver cancer correlates with higher levels of MHC-I molecules in the tumors, and patient survival is directly affected by IRGQ expression levels in CD8+ enriched tumors. Moreover, human T cells are more reactive toward tumorigenic IRGQ knock-out cells. Thus, we reveal IRGQ as a regulator of MHC-I quality control, mediating tumor immune evasion.
HostingRepository	PRIDE
AnnounceDate	2024-11-26
AnnouncementXML	Submission_2024-11-26_04:59:30.242.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Julian Langer
SpeciesList	scientific name: Escherichia coli; NCBI TaxID: 562; scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	Synapt MS

Revision	Datetime	Status	ChangeLog Entry
0	2023-09-08 01:52:00	ID requested
⏵ 1	2024-11-26 04:59:31	announced

10.1016/j.cell.2024.09.048;

Herhaus L, Gestal-Mato U, Eapen VV, Ma, č, inkovi, ć I, Bailey HJ, Prieto-Garcia C, Misra M, Jacomin AC, Ammanath AV, Bagari, ć I, Michaelis J, Vollrath J, Bhaskara RM, B, ü, ndgen G, Covarrubias-Pinto A, Husnjak K, Z, ö, ller J, Gikandi A, Ribi, č, i, ć S, Bopp T, van der Heden van Noort GJ, Langer JD, Weigert A, Harper JW, Mancias JD, Dikic I, IRGQ-mediated autophagy in MHC class I quality control promotes tumor immune evasion. Cell, 187(25):7285-7302.e29(2024) [pubmed]

submitter keyword: HDX-MS, IRGQ, ligand binding

Julian D. Langer
contact affiliation	Max Planck Institute of Biophysics, Frankfurt, Germany
contact email	julian.langer@biophys.mpg.de
lab head
Julian Langer
contact affiliation	MPIs for Biophysics and Brain Research
contact email	julian.langer@biophys.mpg.de
dataset submitter

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2024/11/PXD045212

PRIDE project URI

• PRIDE
  1. PXD045212
     1. Label: PRIDE project
     2. Name: HDX-MS analysis of IRGQ in the presence of GABARAP-L2 and LC3B