NEMO recruitment at single cytokine-receptor complexes shows quantized dynamics independent of ligand affinity.

ABSTRACT: Cells use a limited number of receptors to sense and process molecular information from their environment. In the classical view of signaling, receptor-ligand affinities determine binding kinetics, on timescales of diffusion, where their time-averaged contact duration regulates rapid cytoplasmic signaling events to coordinate cellular responses. For some cytokines, single receptor-ligand binding events can initiate large multiprotein complexes in the cytoplasm that assemble over tens of minutes, raising the question of how cytokine affinity influences the sensitivity and strength of signaling. Here, we leverage naturally occurring variations of interleukin (IL)-1β from multiple species to determine the impact of affinity on human IL-1 receptor signaling. Using experiments and models, we in

SUBMITTER: Kim AH 

PROVIDER: S-EPMC12831165 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature