Identification of a New Cholesterol-Binding Site within the IFN-gamma Receptor that is Required for Signal Transduction
dc.contributor.author | Morana, Ornella | |
dc.contributor.author | Nieto Garai, Jon Ander | |
dc.contributor.author | Bjorkholm, Patrik | |
dc.contributor.author | Bernardino de la Serna, Jorge | |
dc.contributor.author | Terrones Urio, Oihana | |
dc.contributor.author | Arboleya, Aroa | |
dc.contributor.author | Ciceri, Dalila | |
dc.contributor.author | Rojo Bartolomé, Iratxe | |
dc.contributor.author | Blouin, Cedric M. | |
dc.contributor.author | Lamaze, Christophe | |
dc.contributor.author | Lorizate Nogales, Maier | |
dc.contributor.author | Contreras, F. Xabier | |
dc.date.accessioned | 2022-05-13T07:32:05Z | |
dc.date.available | 2022-05-13T07:32:05Z | |
dc.date.issued | 2022 | |
dc.identifier.citation | Advanced Science 9(11) : (2022) // Article ID 2105170 | es_ES |
dc.identifier.issn | 2198-3844 | |
dc.identifier.uri | http://hdl.handle.net/10810/56537 | |
dc.description.abstract | [EN] The cytokine interferon-gamma (IFN-gamma) is a master regulator of innate and adaptive immunity involved in a broad array of human diseases that range from atherosclerosis to cancer. IFN-gamma exerts it signaling action by binding to a specific cell surface receptor, the IFN-gamma receptor (IFN-gamma R), whose activation critically depends on its partition into lipid nanodomains. However, little is known about the impact of specific lipids on IFN-gamma R 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-gamma R2 chains into plasma membrane lipid nanodomains, orchestrating IFN-gamma R 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-gamma R 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-IFN gamma R2 interaction may represent a potential therapeutic strategy for various IFN-gamma-dependent diseases. | es_ES |
dc.description.sponsorship | This work was supported by grants from the Spanish Ministry of Science, Innovation, and Universities (BFU-2015-68981-P and PID2020-117405GB-I00) and the Basque Government (IT1264-19, IT1625-22) to F.-X.C. and M.L. F.-X.C. acknowledge the generous support of Fundacion Ramon Areces (grant CIVP20S11276). O.T. was supported by a Basque Government grant (IT1270-19) I.R.-B., O.M., J.A.N.-G., and D.C. were supported by the Fundacion Biofisica Bizkaia. The Lamaze laboratory was supported from Agence Nationale de la Recherche grants ANR-11-LABX-0038, ANR-10-IDEX-0001-02, and ANR NanoGammaR-15-CE11-0025-01. The Bernardino de la Serna Lab acknowledges support from Belinda and Bill Gates Foundation and BBSRC (INV-016631 and BB/V019791/1, respectively). This work was supported in part by the Fundacion Biofisica Bizkaia and the Basque Excellence Research Centre (BERC) program of the Basque Government. The authors thank J. M. Gonzalez Manas for helpful comments on the manuscript. The authors thank the technical and human support provided by the analytical and high-resolution microscopy facility (SGIker) of UPV/EHU and European funding (ERDF and ESF). | es_ES |
dc.language.iso | eng | es_ES |
dc.publisher | Wiley | es_ES |
dc.relation | info:eu-repo/grantAgreement/MINECO/BFU-2015-68981-P | es_ES |
dc.relation | info:eu-repo/grantAgreement/MICINN/PID2020-117405GB-I00 | es_ES |
dc.rights | info:eu-repo/semantics/openAccess | es_ES |
dc.rights.uri | http://creativecommons.org/licenses/by/3.0/es/ | * |
dc.subject | cholesterol | es_ES |
dc.subject | interferon gamma receptors | es_ES |
dc.subject | lipid nanodomains | es_ES |
dc.subject | protein-lipid interactions | es_ES |
dc.subject | signal transduction | es_ES |
dc.title | Identification of a New Cholesterol-Binding Site within the IFN-gamma Receptor that is Required for Signal Transduction | es_ES |
dc.type | info:eu-repo/semantics/article | es_ES |
dc.rights.holder | © 2022 The Authors. Advanced Science published by Wiley-VCH GmbH This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. | es_ES |
dc.rights.holder | Atribución 3.0 España | * |
dc.relation.publisherversion | https://onlinelibrary.wiley.com/doi/10.1002/advs.202105170 | es_ES |
dc.identifier.doi | 10.1002/advs.202105170 | |
dc.departamentoes | Bioquímica y biología molecular | es_ES |
dc.departamentoeu | Biokimika eta biologia molekularra | es_ES |
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This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.