Monitoring GPCR Conformation with GFP-Inspired Dyes

Belousov, A.; Maslov, I.; Orekhov, P.; Khorn, P.; Kuzmichev, P.; Baleeva, N.; Motov, V.; Bogorodskiy, A.; Krasnova, S.; Mineev, K.; Zinchenko, D.; Zernii, E.; Ivanovich, V.; Permyakov, S.; Hofkens, J.; Hendrix, J.; Cherezov, V.; Gensch, T.; Mishin, A.; Baranov, M.; Mishin, A.; Borshchevskiy, V.

Авторы: Belousov Anatoliy, Maslov Ivan, Orekhov Philipp, Khorn Polina, Kuzmichev Pavel, Baleeva Nadezhda, Motov Vladislav, Bogorodskiy Andrey, Krasnova Svetlana, Mineev Konstantin, Zinchenko Dmitry, Zernii Evgeni, Ivanovich Valentin, Permyakov Sergei, Hofkens Johan, Hendrix Jelle, Cherezov Vadim, Gensch Thomas, Mishin Alexander, Baranov Mikhail, Mishin Alexey, Borshchevskiy Valentin
Журнал: iScience
Год издания: 2024
Издательство: Cell Press
Местоположение издательства: United States
Номер статьи: 110466
DOI: 10.1016/j.isci.2024.110466
Аннотация: Solvatochromic compounds have emerged as valuable environment-sensitive probes for biological research. Here we used thiol-reactive solvatochromic analogues of the green fluorescent protein (GFP) chromophore to track conformational changes in two proteins, recoverin and the A2A adenosine receptor (A2AAR). Two dyes showed Ca2+-induced fluorescence changes when attached to recoverin. Our best-performing dye, DyeC, exhibited agonist-induced changes in both intensity and shape of its fluorescence spectrum when attached to A2AAR; none of these effects were observed with other common environment-sensitive dyes. Molecular dynamics simulations showed that activation of the A2AAR led to a more confined and hydrophilic environment for DyeC. Additionally, an allosteric modulator of A2AAR induced distinct fluorescence changes in the DyeC spectrum, indicating a unique receptor conformation. Our study demonstrated that GFP-inspired dyes are effective for detecting structural changes in G protein-coupled receptors (GPCRs), offering advantages such as intensity-based and ratiometric tracking, red-shifted fluorescence spectra, and sensitivity to allosteric modulation.
Добавил в систему: Зерний Евгений Юрьевич

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Monitoring GPCR Conformation with GFP-Inspired Dyesстатья Исследовательская статья