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 effecto...
| Main Authors: | , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2023-05-01
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| Series: | Frontiers in Endocrinology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fendo.2023.1111594/full |
| _version_ | 1827930920797077504 |
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| author | Roger D. Jones Roger D. Jones Roger D. Jones Alan M. Jones Alan M. Jones |
| author_facet | Roger D. Jones Roger D. Jones Roger D. Jones Alan M. Jones Alan M. Jones |
| author_sort | Roger D. Jones |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-13T06:44:20Z |
| format | Article |
| id | doaj.art-7adbbc0919774a59874fe5505ad8147e |
| institution | Directory Open Access Journal |
| issn | 1664-2392 |
| language | English |
| last_indexed | 2024-03-13T06:44:20Z |
| publishDate | 2023-05-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Endocrinology |
| spelling | doaj.art-7adbbc0919774a59874fe5505ad8147e2023-06-08T12:09:27ZengFrontiers Media S.A.Frontiers in Endocrinology1664-23922023-05-011410.3389/fendo.2023.11115941111594Model of ligand-triggered information transmission in G-protein coupled receptor complexesRoger D. Jones0Roger D. Jones1Roger D. Jones2Alan M. Jones3Alan M. Jones4Department of Biology, University of North Carolina at Chapel Hill, Chapel Hill, NC, United StatesEuropean Centre for Living Technology, Ca’ Foscari University of Venice, Venice, ItalySystems Engineering and Research Center, Stevens Institute of Technology, Hoboken, NJ, United StatesDepartment of Biology, University of North Carolina at Chapel Hill, Chapel Hill, NC, United StatesDepartment of Pharmacology, University of North Carolina at Chapel Hill, Chapel Hill, NC, United StatesWe 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.https://www.frontiersin.org/articles/10.3389/fendo.2023.1111594/fullG protein coupled receptordrug discoveryinformation transmissionmaximum rate of entropy productiontransmembrane receptorbarcode |
| spellingShingle | Roger D. Jones Roger D. Jones Roger D. Jones Alan M. Jones Alan M. Jones Model of ligand-triggered information transmission in G-protein coupled receptor complexes Frontiers in Endocrinology G protein coupled receptor drug discovery information transmission maximum rate of entropy production transmembrane receptor barcode |
| title | Model of ligand-triggered information transmission in G-protein coupled receptor complexes |
| title_full | Model of ligand-triggered information transmission in G-protein coupled receptor complexes |
| title_fullStr | Model of ligand-triggered information transmission in G-protein coupled receptor complexes |
| title_full_unstemmed | Model of ligand-triggered information transmission in G-protein coupled receptor complexes |
| title_short | Model of ligand-triggered information transmission in G-protein coupled receptor complexes |
| title_sort | model of ligand triggered information transmission in g protein coupled receptor complexes |
| topic | G protein coupled receptor drug discovery information transmission maximum rate of entropy production transmembrane receptor barcode |
| url | https://www.frontiersin.org/articles/10.3389/fendo.2023.1111594/full |
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