8Q7K

IRGQ LIR2 peptide in complex with LC3B

8Q7K の概要

• エントリーDOI: 10.2210/pdb8q7k/pdb
• 分子名称: Microtubule-associated proteins 1A/1B light chain 3B, Immunity-related GTPase family Q protein, 1,2-ETHANEDIOL, ... (4 entities in total)
• 機能のキーワード: autophagy, lc3b, lir, irgq, protein binding
• 由来する生物種: Homo sapiens (human); 詳細
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 31780.44

構造登録者

Misra, M.,Bailey, H.J.,Pomirska, J.,Dikic, I. (登録日: 2023-08-16, 公開日: 2024-08-28, 最終更新日: 2025-03-19)

主引用文献

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

実験手法

X-RAY DIFFRACTION (1.6 Å)