Co-Evolution of Opioid and Adrenergic Ligands and Receptors: Shared, Complementary Modules Explain Evolution of Functional Interactions and Suggest Novel Engineering Possibilities

Cross-talk between opioid and adrenergic receptors is well-characterized and involves second messenger systems, the formation of receptor heterodimers, and the presence of extracellular allosteric binding regions for the complementary ligand; however, the evolutionary origins of these interactions h...

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Autores principales:	Robert Root-Bernstein, Beth Churchill
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	receptor–ligand co-evolution opioid adrenergic cross-talk molecular complementarity modular Science Q
Acceso en línea:	https://doaj.org/article/ebbaed48e183491a800d414444cfde4a
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spelling	oai:doaj.org-article:ebbaed48e183491a800d414444cfde4a2021-11-25T18:11:17ZCo-Evolution of Opioid and Adrenergic Ligands and Receptors: Shared, Complementary Modules Explain Evolution of Functional Interactions and Suggest Novel Engineering Possibilities10.3390/life111112172075-1729https://doaj.org/article/ebbaed48e183491a800d414444cfde4a2021-11-01T00:00:00Zhttps://www.mdpi.com/2075-1729/11/11/1217https://doaj.org/toc/2075-1729Cross-talk between opioid and adrenergic receptors is well-characterized and involves second messenger systems, the formation of receptor heterodimers, and the presence of extracellular allosteric binding regions for the complementary ligand; however, the evolutionary origins of these interactions have not been investigated. We propose that opioid and adrenergic ligands and receptors co-evolved from a common set of modular precursors so that they share binding functions. We demonstrate the plausibility of this hypothesis through a review of experimental evidence for molecularly complementary modules and report unexpected homologies between the two receptor types. Briefly, opioids form homodimers also bind adrenergic compounds; opioids bind to conserved extracellular regions of adrenergic receptors while adrenergic compounds bind to conserved extracellular regions of opioid receptors; opioid-like modules appear in both sets of receptors within key ligand-binding regions. Transmembrane regions associated with homodimerization of each class of receptors are also highly conserved across receptor types and implicated in heterodimerization. This conservation of multiple functional modules suggests opioid–adrenergic ligand and receptor co-evolution and provides mechanisms for explaining the evolution of their crosstalk. These modules also suggest the structure of a primordial receptor, providing clues for engineering receptor functions.Robert Root-BernsteinBeth ChurchillMDPI AGarticlereceptor–ligand co-evolutionopioidadrenergiccross-talkmolecular complementaritymodularScienceQENLife, Vol 11, Iss 1217, p 1217 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	receptor–ligand co-evolution opioid adrenergic cross-talk molecular complementarity modular Science Q
spellingShingle	receptor–ligand co-evolution opioid adrenergic cross-talk molecular complementarity modular Science Q Robert Root-Bernstein Beth Churchill Co-Evolution of Opioid and Adrenergic Ligands and Receptors: Shared, Complementary Modules Explain Evolution of Functional Interactions and Suggest Novel Engineering Possibilities
description	Cross-talk between opioid and adrenergic receptors is well-characterized and involves second messenger systems, the formation of receptor heterodimers, and the presence of extracellular allosteric binding regions for the complementary ligand; however, the evolutionary origins of these interactions have not been investigated. We propose that opioid and adrenergic ligands and receptors co-evolved from a common set of modular precursors so that they share binding functions. We demonstrate the plausibility of this hypothesis through a review of experimental evidence for molecularly complementary modules and report unexpected homologies between the two receptor types. Briefly, opioids form homodimers also bind adrenergic compounds; opioids bind to conserved extracellular regions of adrenergic receptors while adrenergic compounds bind to conserved extracellular regions of opioid receptors; opioid-like modules appear in both sets of receptors within key ligand-binding regions. Transmembrane regions associated with homodimerization of each class of receptors are also highly conserved across receptor types and implicated in heterodimerization. This conservation of multiple functional modules suggests opioid–adrenergic ligand and receptor co-evolution and provides mechanisms for explaining the evolution of their crosstalk. These modules also suggest the structure of a primordial receptor, providing clues for engineering receptor functions.
format	article
author	Robert Root-Bernstein Beth Churchill
author_facet	Robert Root-Bernstein Beth Churchill
author_sort	Robert Root-Bernstein
title	Co-Evolution of Opioid and Adrenergic Ligands and Receptors: Shared, Complementary Modules Explain Evolution of Functional Interactions and Suggest Novel Engineering Possibilities
title_short	Co-Evolution of Opioid and Adrenergic Ligands and Receptors: Shared, Complementary Modules Explain Evolution of Functional Interactions and Suggest Novel Engineering Possibilities
title_full	Co-Evolution of Opioid and Adrenergic Ligands and Receptors: Shared, Complementary Modules Explain Evolution of Functional Interactions and Suggest Novel Engineering Possibilities
title_fullStr	Co-Evolution of Opioid and Adrenergic Ligands and Receptors: Shared, Complementary Modules Explain Evolution of Functional Interactions and Suggest Novel Engineering Possibilities
title_full_unstemmed	Co-Evolution of Opioid and Adrenergic Ligands and Receptors: Shared, Complementary Modules Explain Evolution of Functional Interactions and Suggest Novel Engineering Possibilities
title_sort	co-evolution of opioid and adrenergic ligands and receptors: shared, complementary modules explain evolution of functional interactions and suggest novel engineering possibilities
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/ebbaed48e183491a800d414444cfde4a
work_keys_str_mv	AT robertrootbernstein coevolutionofopioidandadrenergicligandsandreceptorssharedcomplementarymodulesexplainevolutionoffunctionalinteractionsandsuggestnovelengineeringpossibilities AT bethchurchill coevolutionofopioidandadrenergicligandsandreceptorssharedcomplementarymodulesexplainevolutionoffunctionalinteractionsandsuggestnovelengineeringpossibilities
_version_	1718411533704232960

Co-Evolution of Opioid and Adrenergic Ligands and Receptors: Shared, Complementary Modules Explain Evolution of Functional Interactions and Suggest Novel Engineering Possibilities

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