Optimal ligand discrimination by asymmetric dimerization and turnover of interferon receptors

• Verfasst von: Binder, Patrick [VerfasserIn]
• Verfasst von: Schnellbächer, Nikolas David [VerfasserIn]
• Verfasst von: Höfer, Thomas [VerfasserIn]
• Verfasst von: Becker, Nils B. [VerfasserIn]
• Verfasst von: Schwarz, Ulrich S. [VerfasserIn]
• Titel: Optimal ligand discrimination by asymmetric dimerization and turnover of interferon receptors
• Verf.angabe: Patrick Binder, Nikolas D. Schnellbächer, Thomas Höfer, Nils B. Becker, and Ulrich S. Schwarz
• E-Jahr: 2021
• Jahr: September 10, 2021
• Umfang: 8 S.
• Fussnoten: Gesehen am 20.10.2021
• Titel Quelle: Enthalten in: National Academy of Sciences (Washington, DC)Proceedings of the National Academy of Sciences of the United States of America
• Ort Quelle: Washington, DC : National Acad. of Sciences, 1915
• Jahr Quelle: 2021
• Band/Heft Quelle: 118(2021), 37, Artikel-ID e2103939118, Seite 1-8
• ISSN Quelle: 1091-6490
• DOI: doi:10.1073/pnas.2103939118
• Datenträger: Online-Ressource
• Sprache: eng
• Sach-SW: cell-cell communication
• Sach-SW: immune response
• Sach-SW: information theory
• Sach-SW: robust sensing
• Sach-SW: signal transduction
• K10plus-PPN: 177460437X

Abstract

In multicellular organisms, antiviral defense mechanisms evoke a reliable collective immune response despite the noisy nature of biochemical communication between tissue cells. A molecular hub of this response, the interferon I receptor (IFNAR), discriminates between ligand types by their affinity regardless of concentration. To understand how ligand type can be decoded robustly by a single receptor, we frame ligand discrimination as an information-theoretic problem and systematically compare the major classes of receptor architectures: allosteric, homodimerizing, and heterodimerizing. We demonstrate that asymmetric heterodimers achieve the best discrimination power over the entire physiological range of local ligand concentrations. This design enables sensing of ligand presence and type, and it buffers against moderate concentration fluctuations. In addition, receptor turnover, which drives the receptor system out of thermodynamic equilibrium, allows alignment of activation points for ligands of different affinities and thereby makes ligand discrimination practically independent of concentration. IFNAR exhibits this optimal architecture, and our findings thus suggest that this specialized receptor can robustly decode digital messages carried by its different ligands.