Dresden 2020 – wissenschaftliches Programm
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BP 10.28: Poster
Montag, 16. März 2020, 17:30–19:30, P2/3OG
Robust ligand discrimination by dimeric membrane receptors — •Patrick Binder1,2,3, Nikolas Schnellbächer1,2, Nils Becker2,3, Thomas Höfer2,3, and Ulrich Schwarz1,2 — 1Institute for Theoretical Physics, Heidelberg University, Heidelberg, Germany — 2BioQuant, Heidelberg University, Heidelberg, Germany — 3Division of Theoretical Systems Biology, German Cancer Research Center, Heidelberg, Germany
Many cytokine pathways transduce signals across the cell membrane via ligand-induced receptor dimerization. As differences in cellular response show, the dimeric Interferon-I receptor system can not only sense ligand concentration, but also discriminate between different types of ligand that all bind to the same receptor type. Here we investigate, using information-theoretic methods, which architectural features optimize the ligand discrimination performance of receptor systems. By defining a basic ligand discrimination task and comparing monomeric, homodimeric and heterodimeric receptors, we find that each step in complexity improves the sensory mutual information. We first observe that monomeric receptors are insufficient to sense the ligand presence and type simultaneously. Second, due to the bell-shaped activation curve, the affinity of dimeric receptors is encoded in the maximal activation. Third, asymmetric binding of ligand to heterodimeric receptors broadens the maximum into a plateau, which buffers concentration fluctuations in the physiological range of the type-I interferon system. Fourth, additional turnover of receptors further steepen the response and broaden the plateau.