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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},
}