8Q7K

IRGQ LIR2 peptide in complex with LC3B

Summary for 8Q7K

• Entry DOI: 10.2210/pdb8q7k/pdb
• Descriptor: Microtubule-associated proteins 1A/1B light chain 3B, Immunity-related GTPase family Q protein, 1,2-ETHANEDIOL, ... (4 entities in total)
• Functional Keywords: autophagy, lc3b, lir, irgq, protein binding
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 4
• Total formula weight: 31780.44

Authors

Misra, M.,Bailey, H.J.,Pomirska, J.,Dikic, I. (deposition date: 2023-08-16, release date: 2024-08-28, Last modification date: 2025-03-19)

Primary citation

Herhaus, L.,Gestal-Mato, U.,Eapen, V.V.,Macinkovic, I.,Bailey, H.J.,Prieto-Garcia, C.,Misra, M.,Jacomin, A.C.,Ammanath, A.V.,Bagaric, I.,Michaelis, J.,Vollrath, J.,Bhaskara, R.M.,Bundgen, G.,Covarrubias-Pinto, A.,Husnjak, K.,Zoller, J.,Gikandi, A.,Ribicic, S.,Bopp, T.,van der Heden van Noort, G.J.,Langer, J.D.,Weigert, A.,Harper, J.W.,Mancias, J.D.,Dikic, I.
IRGQ-mediated autophagy in MHC class I quality control promotes tumor immune evasion.
Cell, 187:7285-7302.e29, 2024

PubMed Abstract: The autophagy-lysosome system directs the degradation of a wide variety of cargo and is also involved in tumor progression. Here, we show that the immunity-related GTPase family Q protein (IRGQ), an uncharacterized protein to date, acts in the quality control of major histocompatibility complex class I (MHC class I) molecules. IRGQ directs misfolded MHC class I toward lysosomal degradation through its binding mode to GABARAPL2 and LC3B. In the absence of IRGQ, free MHC class I heavy chains do not only accumulate in the cell but are also transported to the cell surface, thereby promoting an immune response. Mice and human patients suffering from hepatocellular carcinoma show improved survival rates with reduced IRGQ levels due to increased reactivity of CD8+ T cells toward IRGQ knockout tumor cells. Thus, we reveal IRGQ as a regulator of MHC class I quality control, mediating tumor immune evasion.

PubMed: 39481378
DOI: 10.1016/j.cell.2024.09.048

Experimental method

X-RAY DIFFRACTION (1.6 Å)