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

Frontiers in Endocrinology

Endocrinology

Alan M. Jones¹  Roger D. Jones² 

[1] Department of Biology, University of North Carolina at Chapel Hill, Chapel Hill, NC, United States;Department of Pharmacology, University of North Carolina at Chapel Hill, Chapel Hill, NC, United States;Department of Biology, University of North Carolina at Chapel Hill, Chapel Hill, NC, United States;European Centre for Living Technology, Ca’ Foscari University of Venice, Venice, Italy;Systems Engineering and Research Center, Stevens Institute of Technology, Hoboken, NJ, United States;

关键词: G protein coupled receptor;    drug discovery;    information transmission;    maximum rate of entropy production;    transmembrane receptor;    barcode;    flute model;    QR code;   

DOI  :  10.3389/fendo.2023.1111594

 received in 2022-11-29, accepted in 2023-03-21,  发布年份 2023

来源: Frontiers

【 摘 要 】

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.

【 授权许可】

Unknown   
Copyright © 2023 Jones and Jones