Model of ligand-triggered information transmission in G-protein coupled receptor complexes

We present a model for the effects of ligands on information transmission in G-Protein Coupled Receptor (GPCR) complexes. The model is built ab initio entirely on principles of statistical mechanics and tenets of information transmission theory and was validated in part using agonist-induced effector activity and signaling bias for the angiotensin- and adrenergic-mediated signaling pathways, with in vitro observations of phosphorylation sites on the C tail of the GPCR complex, and single-cell information-transmission experiments. The model extends traditional kinetic models that form the basis for many existing models of GPCR signaling. It is based on maximizing the rates of entropy production and information transmission through the GPCR complex. The model predicts that (1) phosphatase-catalyzed reactions, as opposed to kinase-catalyzed reactions, on the C-tail and internal loops of the GPCR are responsible for controlling the signaling activity, (2) signaling favors the statistical balance of the number of switches in the ON state and the number in the OFF state, and (3) biased-signaling response depends discontinuously on ligand concentration.

Automated summary

We propose a model that examines the effects of ligands on information transmission in G-Protein Coupled Receptor(GPCR) complexes. The model is based on statistical mechanics and information transmission theory and was validated through in vitro observations and single-cell experiments. The model predicts the role of phosphatase-catalyzed reactions in controlling signaling activity, the statistical balance between ON and OFF switches in signaling, and the discontinuous relationship between biased-signaling response and ligand concentration.