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Identification of a New Cholesterol‐Binding Site within the IFN‐γ Receptor that is Required for Signal Transduction
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 activ...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9008429/ https://www.ncbi.nlm.nih.gov/pubmed/35166455 http://dx.doi.org/10.1002/advs.202105170 |
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author | Morana, Ornella Nieto‐Garai, Jon Ander Björkholm, Patrik Bernardino de la Serna, Jorge Terrones, Oihana Arboleya, Aroa Ciceri, Dalila Rojo‐Bartolomé, Iratxe Blouin, Cédric M. Lamaze, Christophe Lorizate, Maier Contreras, Francesc‐Xabier |
author_facet | Morana, Ornella Nieto‐Garai, Jon Ander Björkholm, Patrik Bernardino de la Serna, Jorge Terrones, Oihana Arboleya, Aroa Ciceri, Dalila Rojo‐Bartolomé, Iratxe Blouin, Cédric M. Lamaze, Christophe Lorizate, Maier Contreras, Francesc‐Xabier |
author_sort | Morana, Ornella |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-9008429 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-90084292022-04-15 Identification of a New Cholesterol‐Binding Site within the IFN‐γ Receptor that is Required for Signal Transduction Morana, Ornella Nieto‐Garai, Jon Ander Björkholm, Patrik Bernardino de la Serna, Jorge Terrones, Oihana Arboleya, Aroa Ciceri, Dalila Rojo‐Bartolomé, Iratxe Blouin, Cédric M. Lamaze, Christophe Lorizate, Maier Contreras, Francesc‐Xabier Adv Sci (Weinh) Research Articles 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. John Wiley and Sons Inc. 2022-02-15 /pmc/articles/PMC9008429/ /pubmed/35166455 http://dx.doi.org/10.1002/advs.202105170 Text en © 2022 The Authors. Advanced Science published by Wiley‐VCH GmbH https://creativecommons.org/licenses/by/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Articles Morana, Ornella Nieto‐Garai, Jon Ander Björkholm, Patrik Bernardino de la Serna, Jorge Terrones, Oihana Arboleya, Aroa Ciceri, Dalila Rojo‐Bartolomé, Iratxe Blouin, Cédric M. Lamaze, Christophe Lorizate, Maier Contreras, Francesc‐Xabier Identification of a New Cholesterol‐Binding Site within the IFN‐γ Receptor that is Required for Signal Transduction |
title | Identification of a New Cholesterol‐Binding Site within the IFN‐γ Receptor that is Required for Signal Transduction |
title_full | Identification of a New Cholesterol‐Binding Site within the IFN‐γ Receptor that is Required for Signal Transduction |
title_fullStr | Identification of a New Cholesterol‐Binding Site within the IFN‐γ Receptor that is Required for Signal Transduction |
title_full_unstemmed | Identification of a New Cholesterol‐Binding Site within the IFN‐γ Receptor that is Required for Signal Transduction |
title_short | Identification of a New Cholesterol‐Binding Site within the IFN‐γ Receptor that is Required for Signal Transduction |
title_sort | identification of a new cholesterol‐binding site within the ifn‐γ receptor that is required for signal transduction |
topic | Research Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9008429/ https://www.ncbi.nlm.nih.gov/pubmed/35166455 http://dx.doi.org/10.1002/advs.202105170 |
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