Regensburg 2022 – scientific programme
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BP: Fachverband Biologische Physik
BP 24: Systems Biology, Gene Expression, Signalling
BP 24.3: Talk
Thursday, September 8, 2022, 11:15–11:30, H16
Optimal ligand discrimination by asymmetric dimerization of interferon receptors — •Patrick Binder1,2,3, Nikolas D. Schnellbächer1,2, Thomas Höfer2,3, Nils B. Becker2,3, and Ulrich S. Schwarz1,2 — 1Institute for Theoretical Physics, Heidelberg University, 69120 Heidelberg, Germany — 2BioQuant Center for Quantitative Biology, Heidelberg University, 69120 Heidelberg, Germany — 3Theoretical Systems Biology, German Cancer Research Center, 69120 Heidelberg, Germany
In multicellular organisms, antiviral defense is mediated by ligands. These signaling molecules are usually characterized by highly inhomogeneous distributions due to scarcity of producer cells, diffusion and localized degradation. And yet, a molecular hub of the antiviral response, the interferon I receptor (IFNAR), discriminates between ligand types by their affinity regardless of concentration. In my talk, I address the long-standing question of how a single receptor can decode robustly ligand type. I frame ligand discrimination as an information-theoretic problem and systematically compare the major classes of receptor architectures: allosteric, homodimerizing, and heterodimerizing. As a result, asymmetric heterodimers achieve the best discrimination power over the entire physiological range of local ligand concentrations, enabling sensing of ligand presence and type. IFNAR exhibits this optimal architecture, suggesting that it has evolved the optimal design to detect and separate the presence of different ligand types in a noisy environment.