Identification of a New Cholesterol-Binding Site within the IFN-γ Receptor that is Required for Signal Transduction.

Autor:	Morana O; Instituto Biofisika (UPV/EHU, CSIC), University of the Basque Country (UPV/EHU), Barrio Sarriena s/n, Leioa, E-48940, Spain.; Fundación Biofísica Bizkaia/Biofisika Bizkaia Fundazioa (FBB), University of the Basque Country (UPV/EHU), Barrio Sarriena s/n, Leioa, E-48940, Spain.; Department of Biochemistry and Molecular Biology, Faculty of Science and Technology, University of the Basque Country (UPV/EHU), Barrio Sarriena s/n, Leioa, E-48940, Spain., Nieto-Garai JA; Instituto Biofisika (UPV/EHU, CSIC), University of the Basque Country (UPV/EHU), Barrio Sarriena s/n, Leioa, E-48940, Spain.; Fundación Biofísica Bizkaia/Biofisika Bizkaia Fundazioa (FBB), University of the Basque Country (UPV/EHU), Barrio Sarriena s/n, Leioa, E-48940, Spain.; Department of Biochemistry and Molecular Biology, Faculty of Science and Technology, University of the Basque Country (UPV/EHU), Barrio Sarriena s/n, Leioa, E-48940, Spain., Björkholm P; Center for Biomembrane Research, Department of Biochemistry and Biophysics, Stockholm University, Stockholm, SE-106 91, Sweden.; Science for Life Laboratory, Stockholm University, Solna, SE-171 21, Sweden., Bernardino de la Serna J; National Heart and Lung Institute, Faculty of Medicine, Imperial College London, South Kensington, Sir Alexander Fleming Building, London, SW7 2AZ, UK.; Central Laser Facility, Rutherford Appleton Laboratory, MRC-Research Complex at Harwell, Science and Technology Facilities Council, Harwell, OX11 0QX, UK.; NIHR Imperial Biomedical Research Centre, London, SW7 2AZ, UK., Terrones O; Department of Biochemistry and Molecular Biology, Faculty of Science and Technology, University of the Basque Country (UPV/EHU), Barrio Sarriena s/n, Leioa, E-48940, Spain., Arboleya A; Instituto Biofisika (UPV/EHU, CSIC), University of the Basque Country (UPV/EHU), Barrio Sarriena s/n, Leioa, E-48940, Spain.; Fundación Biofísica Bizkaia/Biofisika Bizkaia Fundazioa (FBB), University of the Basque Country (UPV/EHU), Barrio Sarriena s/n, Leioa, E-48940, Spain.; Department of Biochemistry and Molecular Biology, Faculty of Science and Technology, University of the Basque Country (UPV/EHU), Barrio Sarriena s/n, Leioa, E-48940, Spain., Ciceri D; Instituto Biofisika (UPV/EHU, CSIC), University of the Basque Country (UPV/EHU), Barrio Sarriena s/n, Leioa, E-48940, Spain.; Fundación Biofísica Bizkaia/Biofisika Bizkaia Fundazioa (FBB), University of the Basque Country (UPV/EHU), Barrio Sarriena s/n, Leioa, E-48940, Spain.; Department of Biochemistry and Molecular Biology, Faculty of Science and Technology, University of the Basque Country (UPV/EHU), Barrio Sarriena s/n, Leioa, E-48940, Spain., Rojo-Bartolomé I; Instituto Biofisika (UPV/EHU, CSIC), University of the Basque Country (UPV/EHU), Barrio Sarriena s/n, Leioa, E-48940, Spain.; Fundación Biofísica Bizkaia/Biofisika Bizkaia Fundazioa (FBB), University of the Basque Country (UPV/EHU), Barrio Sarriena s/n, Leioa, E-48940, Spain.; Department of Biochemistry and Molecular Biology, Faculty of Science and Technology, University of the Basque Country (UPV/EHU), Barrio Sarriena s/n, Leioa, E-48940, Spain., Blouin CM; Institut Curie - Centre de Recherche, PSL Research University, Membrane Mechanics and Dynamics of Intracellular Signaling Laboratory, Paris, 75248, France.; Institut National de la Santé et de la Recherche Médicale (INSERM), Paris, U1143, France.; Centre National de la Recherche Scientifique (CNRS), UMR 3666, Paris, 75248, France., Lamaze C; Institut Curie - Centre de Recherche, PSL Research University, Membrane Mechanics and Dynamics of Intracellular Signaling Laboratory, Paris, 75248, France.; Institut National de la Santé et de la Recherche Médicale (INSERM), Paris, U1143, France.; Centre National de la Recherche Scientifique (CNRS), UMR 3666, Paris, 75248, France., Lorizate M; Instituto Biofisika (UPV/EHU, CSIC), University of the Basque Country (UPV/EHU), Barrio Sarriena s/n, Leioa, E-48940, Spain.; Department of Biochemistry and Molecular Biology, Faculty of Science and Technology, University of the Basque Country (UPV/EHU), Barrio Sarriena s/n, Leioa, E-48940, Spain., Contreras FX; Instituto Biofisika (UPV/EHU, CSIC), University of the Basque Country (UPV/EHU), Barrio Sarriena s/n, Leioa, E-48940, Spain.; Department of Biochemistry and Molecular Biology, Faculty of Science and Technology, University of the Basque Country (UPV/EHU), Barrio Sarriena s/n, Leioa, E-48940, Spain.; IKERBASQUE, Basque Foundation for Science, Bilbao, 48011, Spain.
Jazyk:	angličtina
Zdroj:	Advanced science (Weinheim, Baden-Wurttemberg, Germany) [Adv Sci (Weinh)] 2022 Apr; Vol. 9 (11), pp. e2105170. Date of Electronic Publication: 2022 Feb 15.
DOI:	10.1002/advs.202105170
Abstrakt:	The cytokine interferon-gamma (IFN-γ) is a master regulator of innate and adaptive immunity involved in a broad array of human diseases that range from atherosclerosis to cancer. IFN-γ exerts it signaling action by binding to a specific cell surface receptor, the IFN-γ receptor (IFN-γR), whose activation critically depends on its partition into lipid nanodomains. However, little is known about the impact of specific lipids on IFN-γR signal transduction activity. Here, a new conserved cholesterol (chol) binding motif localized within its single transmembrane domain is identified. Through direct binding, chol drives the partition of IFN-γR2 chains into plasma membrane lipid nanodomains, orchestrating IFN-γR oligomerization and transmembrane signaling. Bioinformatics studies show that the signature sequence stands for a conserved chol-binding motif presented in many mammalian membrane proteins. The discovery of chol as the molecular switch governing IFN-γR transmembrane signaling represents a significant advance for understanding the mechanism of lipid selectivity by membrane proteins, but also for figuring out the role of lipids in modulating cell surface receptor function. Finally, this study suggests that inhibition of the chol-IFNγR2 interaction may represent a potential therapeutic strategy for various IFN-γ-dependent diseases. (© 2022 The Authors. Advanced Science published by Wiley-VCH GmbH.)
Databáze:	MEDLINE
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