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@ARTICLE{Maslov:1021291,
author = {Maslov, Ivan and Volkov, Oleksandr and Khorn, Polina and
Orekhov, Philipp and Gusach, Anastasiia and Kuzmichev, Pavel
and Gerasimov, Andrey and Luginina, Aleksandra and Coucke,
Quinten and Bogorodskiy, Andrey and Gordeliy, Valentin and
Wanninger, Simon and Barth, Anders and Mishin, Alexey and
Hofkens, Johan and Cherezov, Vadim and Gensch, Thomas and
Hendrix, Jelle and Borshchevskiy, Valentin},
title = {{S}ub-millisecond conformational dynamics of the {A}2{A}
adenosine receptor revealed by single-molecule {FRET}},
journal = {Communications biology},
volume = {6},
number = {1},
issn = {2399-3642},
address = {London},
publisher = {Springer Nature},
reportid = {FZJ-2024-00721},
pages = {362},
year = {2023},
note = {A.L., A.B., and V.B. are thankful for the Ministry of
Science and Higher Education of theRussian Federation
(agreement #075-03-2023-106, project FSMG-2020-0003).
IMacknowledges the UHasselt Special Research Fund.
Measurements of surface expressionand Gs-signaling were
supported by the Russian Science Foundation (project no.
22-74-10036; https://rscf.ru/project/22-74-10036/).
Computational simulations were supportedby the National
Natural Science Foundation of China, grant #32250410316 (to
PO). Weacknowledge the Advanced Optical Microscopy Centre at
Hasselt University for supportwith microscopy experiments.
Microscopy was made possible by the Research Foundation
Flanders (FWO, projects G0B4915, G0B9922N, and G0H3716N).},
abstract = {The complex pharmacology of G-protein-coupled receptors
(GPCRs) is defined by their multi-state conformational
dynamics. Single-molecule Förster Resonance Energy Transfer
(smFRET) is well suited to quantify dynamics for individual
protein molecules; however, its application to GPCRs is
challenging. Therefore, smFRET has been limited to studies
of inter-receptor interactions in cellular membranes and
receptors in detergent environments. Here, we performed
smFRET experiments on functionally active human A2A
adenosine receptor (A2AAR) molecules embedded in freely
diffusing lipid nanodiscs to study their intramolecular
conformational dynamics. We propose a dynamic model of A2AAR
activation that involves a slow (>2 ms) exchange between
the active-like and inactive-like conformations in both apo
and antagonist-bound A2AAR, explaining the receptor’s
constitutive activity. For the agonist-bound A2AAR, we
detected faster (390 ± 80 µs) ligand
efficacy-dependent dynamics. Our work establishes a general
smFRET platform for GPCR investigations that can potentially
be used for drug screening and/or mechanism-of-action
studies.},
cin = {IBI-1 / IBI-7},
ddc = {570},
cid = {I:(DE-Juel1)IBI-1-20200312 / I:(DE-Juel1)IBI-7-20200312},
pnm = {5244 - Information Processing in Neuronal Networks
(POF4-524)},
pid = {G:(DE-HGF)POF4-5244},
typ = {PUB:(DE-HGF)16},
pubmed = {37012383},
UT = {WOS:000962868600002},
doi = {10.1038/s42003-023-04727-z},
url = {https://juser.fz-juelich.de/record/1021291},
}