ArticleProceedings of the National Academy of Sciences of the United States of America2021
Optimal ligand discrimination by asymmetric dimerization and turnover of interferon receptors.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.
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Who cites it
6 citing papers in PubMed.
- Receptor dimerization enables ligand discrimination through tunable response heterogeneity.PLoS computational biology · 2025Article
- Ligand discrimination in immune cells: Signal processing insights into immune dysfunction in ER+ breast cancer.PLoS computational biology · 2025Article
- DNA microbeads for spatio-temporally controlled morphogen release within organoids.Nature nanotechnology · 2024Article
- Dual-color DNA-PAINT single-particle tracking enables extended studies of membrane protein interactions.Nature communications · 2023Article
- Proofreading does not result in more reliable ligand discrimination in receptor signaling due to its inherent stochasticity.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Deciphering signal transduction networks in the liver by mechanistic mathematical modelling.The Biochemical journal · 2022Article
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Authors and funding
5 authors.
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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.
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