Allosteric interactions within the AT₁ angiotensin receptor homodimer: role of the conserved DRY motif

Biochemical Pharmacology
Bence SzalaiLászló Hunyady

Abstract

G protein coupled receptor (GPCR) dimerization has a remarkable impact on the diversity of receptor signaling. Allosteric communication between the protomers of the dimer can alter ligand binding, receptor conformation and interactions with different effector proteins. In this study we investigated the allosteric interactions between wild type and mutant protomers of type 1 angiotensin receptor (AT₁R) dimers transiently expressed in CHO cells. In our experimental setup, one protomer of the dimer was selectively stimulated and the β-arrestin2 binding and conformation alteration of the other protomer was followed. The interaction between β-arrestin2 and the non-stimulated protomer was monitored through a bioluminescence resonance energy transfer (BRET) based method. To measure the conformational alterations in the non-stimulated protomer directly, we also used a BRET based intramolecular receptor biosensor, which was created by inserting yellow fluorescent protein (YFP) into the 3rd intracellular loop of AT₁R and fusing Renilla luciferase (RLuc) to its C terminal region. We have detected β-arrestin2 binding, and altered conformation of the non-stimulated protomer. The cooperative ligand binding of the receptor homodimer was also ...Continue Reading

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Citations

Jul 12, 2014·Journal of Molecular Endocrinology·Pitchai Balakumar, Gowraganahalli Jagadeesh
Dec 4, 2014·Proceedings of the National Academy of Sciences of the United States of America·Irina KufarevaTracy M Handel
Jun 7, 2018·Physiological Reviews·Steven J ForresterSatoru Eguchi
Apr 27, 2019·Frontiers in Pharmacology·Estefanía MorenoEnric Canela
Mar 6, 2019·Frontiers in Endocrinology·Diego GuidolinLuigi F Agnati
Nov 13, 2015·British Journal of Pharmacology·A D Stumpf, C Hoffmann
May 28, 2021·Frontiers in Cell and Developmental Biology·Yiwei ZhouJianfeng Liu
Jul 3, 2021·International Journal of Molecular Sciences·Céline DelaitreFrançois Dupuis
Aug 21, 2019·Journal of Chemical Information and Modeling·Ismail ErolSerdar Durdagi

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