Электронный каталог

Статья

Maslov, I.
Sub-Millisecond Conformational Dynamics of the A&sub(2A) Adenosine Receptor Revealed by Single-Molecule FRET / I.Maslov, V.Borshchevskiy, [a.o.] // Communications Biology [Electronic resource]. – 2023. – Vol.6. – P.362. – URL: https://doi.org/10.1038/s42003-023-04727-z. – Bibliogr.:107.

The complex pharmacology of G-protein-coupled receptors (GPCRs) is defined by theirmulti-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 A&sub(2A) adenosine receptor(A&sub(2A)AR) molecules embedded in freely diffusing lipid nanodiscs to study their intramolecular conformational dynamics. We propose a dynamic model of A&sub(2A)AR activation that involves aslow (>2 ms) exchange between the active-like and inactive-like conformations in both apo and antagonist-bound A&sub(2A)AR, explaining the receptor’s constitutive activity. For the agonist-bound A&sub(2A)AR, we detected faster (390 ± 80μs) ligand efficacy-dependent dynamics. Ourwork establishes a general smFRET platform for GPCR investigations that can potentially be used for drug screening and/or mechanism-of-action studies.



ОИЯИ = ОИЯИ (JINR)2023
Спец.(статьи,препринты) = 28.0 - Биология$
Спец.(статьи,препринты) = С 350 - Приложения методов ядерной физики в смежных областях
Бюллетени = 7/024