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Bringing GPCR Structural Biology to Medical Applications: Insights from Both V2 Vasopressin and Mu-Opioid Receptors

G-protein coupled receptors (GPCRs) are versatile signaling proteins that regulate key physiological processes in response to a wide variety of extracellular stimuli. The last decade has seen a revolution in the structural biology of clinically important GPCRs. Indeed, the improvement in molecular a...

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Autores principales: Fouillen, Aurélien, Bous, Julien, Granier, Sébastien, Mouillac, Bernard, Sounier, Remy
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10303988/
https://www.ncbi.nlm.nih.gov/pubmed/37367810
http://dx.doi.org/10.3390/membranes13060606
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author Fouillen, Aurélien
Bous, Julien
Granier, Sébastien
Mouillac, Bernard
Sounier, Remy
author_facet Fouillen, Aurélien
Bous, Julien
Granier, Sébastien
Mouillac, Bernard
Sounier, Remy
author_sort Fouillen, Aurélien
collection PubMed
description G-protein coupled receptors (GPCRs) are versatile signaling proteins that regulate key physiological processes in response to a wide variety of extracellular stimuli. The last decade has seen a revolution in the structural biology of clinically important GPCRs. Indeed, the improvement in molecular and biochemical methods to study GPCRs and their transducer complexes, together with advances in cryo-electron microscopy, NMR development, and progress in molecular dynamic simulations, have led to a better understanding of their regulation by ligands of different efficacy and bias. This has also renewed a great interest in GPCR drug discovery, such as finding biased ligands that can either promote or not promote specific regulations. In this review, we focus on two therapeutically relevant GPCR targets, the V2 vasopressin receptor (V2R) and the mu-opioid receptor (µOR), to shed light on the recent structural biology studies and show the impact of this integrative approach on the determination of new potential clinical effective compounds.
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spelling pubmed-103039882023-06-29 Bringing GPCR Structural Biology to Medical Applications: Insights from Both V2 Vasopressin and Mu-Opioid Receptors Fouillen, Aurélien Bous, Julien Granier, Sébastien Mouillac, Bernard Sounier, Remy Membranes (Basel) Review G-protein coupled receptors (GPCRs) are versatile signaling proteins that regulate key physiological processes in response to a wide variety of extracellular stimuli. The last decade has seen a revolution in the structural biology of clinically important GPCRs. Indeed, the improvement in molecular and biochemical methods to study GPCRs and their transducer complexes, together with advances in cryo-electron microscopy, NMR development, and progress in molecular dynamic simulations, have led to a better understanding of their regulation by ligands of different efficacy and bias. This has also renewed a great interest in GPCR drug discovery, such as finding biased ligands that can either promote or not promote specific regulations. In this review, we focus on two therapeutically relevant GPCR targets, the V2 vasopressin receptor (V2R) and the mu-opioid receptor (µOR), to shed light on the recent structural biology studies and show the impact of this integrative approach on the determination of new potential clinical effective compounds. MDPI 2023-06-16 /pmc/articles/PMC10303988/ /pubmed/37367810 http://dx.doi.org/10.3390/membranes13060606 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Review
Fouillen, Aurélien
Bous, Julien
Granier, Sébastien
Mouillac, Bernard
Sounier, Remy
Bringing GPCR Structural Biology to Medical Applications: Insights from Both V2 Vasopressin and Mu-Opioid Receptors
title Bringing GPCR Structural Biology to Medical Applications: Insights from Both V2 Vasopressin and Mu-Opioid Receptors
title_full Bringing GPCR Structural Biology to Medical Applications: Insights from Both V2 Vasopressin and Mu-Opioid Receptors
title_fullStr Bringing GPCR Structural Biology to Medical Applications: Insights from Both V2 Vasopressin and Mu-Opioid Receptors
title_full_unstemmed Bringing GPCR Structural Biology to Medical Applications: Insights from Both V2 Vasopressin and Mu-Opioid Receptors
title_short Bringing GPCR Structural Biology to Medical Applications: Insights from Both V2 Vasopressin and Mu-Opioid Receptors
title_sort bringing gpcr structural biology to medical applications: insights from both v2 vasopressin and mu-opioid receptors
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10303988/
https://www.ncbi.nlm.nih.gov/pubmed/37367810
http://dx.doi.org/10.3390/membranes13060606
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