دورية أكاديمية
A Cholesterol-Based Allostery Model of T Cell Receptor Phosphorylation.
| العنوان: | A Cholesterol-Based Allostery Model of T Cell Receptor Phosphorylation. |
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| المؤلفون: | Swamy M; Department of Immunology, BIOSS Centre for Biological Signalling Studies, Faculty of Biology, and Centre for Chronic Immunodeficiency CCI, University Clinics Freiburg and Medical Faculty, Albert-Ludwigs-University of Freiburg, 79104 Freiburg, Germany; Max Planck-Institute of Immunbiology and Epigenetics, 79108 Freiburg, Germany; Division of Cell Signalling and Immunology, College of Life Sciences, University of Dundee, DD1 5EH, United Kingdom., Beck-Garcia K; Department of Immunology, BIOSS Centre for Biological Signalling Studies, Faculty of Biology, and Centre for Chronic Immunodeficiency CCI, University Clinics Freiburg and Medical Faculty, Albert-Ludwigs-University of Freiburg, 79104 Freiburg, Germany; Max Planck-Institute of Immunbiology and Epigenetics, 79108 Freiburg, Germany; Spemann Graduate School of Biology and Medicine, Albert-Ludwigs-University Freiburg, 79104 Freiburg, Germany., Beck-Garcia E; Department of Immunology, BIOSS Centre for Biological Signalling Studies, Faculty of Biology, and Centre for Chronic Immunodeficiency CCI, University Clinics Freiburg and Medical Faculty, Albert-Ludwigs-University of Freiburg, 79104 Freiburg, Germany; Max Planck-Institute of Immunbiology and Epigenetics, 79108 Freiburg, Germany; International Max Planck-Research School for Molecular and Cellular Biology, 79108 Freiburg, Germany., Hartl FA; Department of Immunology, BIOSS Centre for Biological Signalling Studies, Faculty of Biology, and Centre for Chronic Immunodeficiency CCI, University Clinics Freiburg and Medical Faculty, Albert-Ludwigs-University of Freiburg, 79104 Freiburg, Germany., Morath A; Department of Immunology, BIOSS Centre for Biological Signalling Studies, Faculty of Biology, and Centre for Chronic Immunodeficiency CCI, University Clinics Freiburg and Medical Faculty, Albert-Ludwigs-University of Freiburg, 79104 Freiburg, Germany; Spemann Graduate School of Biology and Medicine, Albert-Ludwigs-University Freiburg, 79104 Freiburg, Germany., Yousefi OS; Department of Immunology, BIOSS Centre for Biological Signalling Studies, Faculty of Biology, and Centre for Chronic Immunodeficiency CCI, University Clinics Freiburg and Medical Faculty, Albert-Ludwigs-University of Freiburg, 79104 Freiburg, Germany; Spemann Graduate School of Biology and Medicine, Albert-Ludwigs-University Freiburg, 79104 Freiburg, Germany., Dopfer EP; Max Planck-Institute of Immunbiology and Epigenetics, 79108 Freiburg, Germany., Molnár E; Department of Immunology, BIOSS Centre for Biological Signalling Studies, Faculty of Biology, and Centre for Chronic Immunodeficiency CCI, University Clinics Freiburg and Medical Faculty, Albert-Ludwigs-University of Freiburg, 79104 Freiburg, Germany., Schulze AK; Division of Theoretical Systems Biology, German Cancer Research Center, 69120 Heidelberg, Germany; BioQuant Center, University of Heidelberg, 69120 Heidelberg, Germany., Blanco R; Centro de Biología Molecular Severo Ochoa, Consejo Superior de Investigaciones Científicas - Universidad Autónoma de Madrid, 28049 Madrid, Spain., Borroto A; Centro de Biología Molecular Severo Ochoa, Consejo Superior de Investigaciones Científicas - Universidad Autónoma de Madrid, 28049 Madrid, Spain., Martín-Blanco N; Centro de Biología Molecular Severo Ochoa, Consejo Superior de Investigaciones Científicas - Universidad Autónoma de Madrid, 28049 Madrid, Spain., Alarcon B; Centro de Biología Molecular Severo Ochoa, Consejo Superior de Investigaciones Científicas - Universidad Autónoma de Madrid, 28049 Madrid, Spain., Höfer T; Division of Theoretical Systems Biology, German Cancer Research Center, 69120 Heidelberg, Germany; BioQuant Center, University of Heidelberg, 69120 Heidelberg, Germany., Minguet S; Department of Immunology, BIOSS Centre for Biological Signalling Studies, Faculty of Biology, and Centre for Chronic Immunodeficiency CCI, University Clinics Freiburg and Medical Faculty, Albert-Ludwigs-University of Freiburg, 79104 Freiburg, Germany; Max Planck-Institute of Immunbiology and Epigenetics, 79108 Freiburg, Germany., Schamel WW; Department of Immunology, BIOSS Centre for Biological Signalling Studies, Faculty of Biology, and Centre for Chronic Immunodeficiency CCI, University Clinics Freiburg and Medical Faculty, Albert-Ludwigs-University of Freiburg, 79104 Freiburg, Germany; Max Planck-Institute of Immunbiology and Epigenetics, 79108 Freiburg, Germany. Electronic address: wolfgang.schamel@biologie.uni-freiburg.de. |
| المصدر: | Immunity [Immunity] 2016 May 17; Vol. 44 (5), pp. 1091-101. |
| نوع المنشور: | Journal Article; Research Support, Non-U.S. Gov't |
| اللغة: | English |
| بيانات الدورية: | Publisher: Cell Press Country of Publication: United States NLM ID: 9432918 Publication Model: Print Cited Medium: Internet ISSN: 1097-4180 (Electronic) Linking ISSN: 10747613 NLM ISO Abbreviation: Immunity Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: Cambridge, MA : Cell Press Original Publication: Cambridge, Mass. : Cell Press, c1994- |
| مواضيع طبية MeSH: | Adaptive Immunity*, Cholesterol/*metabolism , Receptors, Antigen, T-Cell, alpha-beta/*metabolism , T-Lymphocytes/*immunology, Allosteric Regulation ; Antigens/immunology ; Antigens/metabolism ; Histocompatibility Antigens/metabolism ; Humans ; Jurkat Cells ; Lymphocyte Activation ; Models, Immunological ; Peptide Fragments/immunology ; Peptide Fragments/metabolism ; Phosphorylation ; Protein Binding ; Protein Conformation ; Protein Stability ; Signal Transduction |
| مستخلص: | Signaling through the T cell receptor (TCR) controls adaptive immune responses. Antigen binding to TCRαβ transmits signals through the plasma membrane to induce phosphorylation of the CD3 cytoplasmic tails by incompletely understood mechanisms. Here we show that cholesterol bound to the TCRβ transmembrane region keeps the TCR in a resting, inactive conformation that cannot be phosphorylated by active kinases. Only TCRs that spontaneously detached from cholesterol could switch to the active conformation (termed primed TCRs) and then be phosphorylated. Indeed, by modulating cholesterol binding genetically or enzymatically, we could switch the TCR between the resting and primed states. The active conformation was stabilized by binding to peptide-MHC, which thus controlled TCR signaling. These data are explained by a model of reciprocal allosteric regulation of TCR phosphorylation by cholesterol and ligand binding. Our results provide both a molecular mechanism and a conceptual framework for how lipid-receptor interactions regulate signal transduction. (Copyright © 2016 Elsevier Inc. All rights reserved.) |
| معلومات مُعتمدة: | 334763 International ERC_ European Research Council |
| المشرفين على المادة: | 0 (Antigens) 0 (Histocompatibility Antigens) 0 (Peptide Fragments) 0 (Receptors, Antigen, T-Cell, alpha-beta) 97C5T2UQ7J (Cholesterol) |
| تواريخ الأحداث: | Date Created: 20160519 Date Completed: 20170915 Latest Revision: 20210924 |
| رمز التحديث: | 20221213 |
| DOI: | 10.1016/j.immuni.2016.04.011 |
| PMID: | 27192576 |
| قاعدة البيانات: | MEDLINE |
Full Text Finder | تدمد: | 1097-4180 |
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| DOI: | 10.1016/j.immuni.2016.04.011 |