Journal Article

FZJ-2026-01999

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png ABEL-FRET bridges the timescale gap in single-molecule measurements of the structural dynamics in the A2A adenosine receptor

Maslov, I. ; Borshchevskiy, V. ; Pérez, I. ; Cherezov, V. ; Hofkens, J. ; Hendrix, J. ; Börsch, M. (Corresponding author) ; Gensch, T. (Corresponding author)FZJ*

2026
Macmillan Publishers Limited, part of Springer Nature [London]

This record in other databases:  

Please use a persistent id in citations: doi:10.1038/s42004-026-01941-8  doi:10.34734/FZJ-2026-01999

Abstract: The functional complexity of G protein-coupled receptors (GPCRs) arises from their structuraldynamics, spanning timescales from nanoseconds to minutes. Single-molecule Förster ResonanceEnergy Transfer (smFRET) enables direct observation of these dynamics in individual receptors, eitherfreely diffusing in solution, using confocal microscopy, or immobilized on surfaces, using Total InternalReflection Fluorescence (TIRF) camera-based microscopy. However, these modalities are limited todistinct timescales – faster than milliseconds or slower than hundreds of milliseconds, respectively. Toovercome these limitations, we employed smFRET with Anti-Brownian Electrokinetic (ABEL) trappingto extend the observation time of untethered human A2A adenosine receptors (A2AAR) reconstituted inlipid nanodiscs from milliseconds to seconds. We characterized conformational heterogeneity in apoand ligand-bound A2AAR and updated previous estimates of dwell times for long-lived receptor statesfrom milliseconds to hundreds of milliseconds. Our results highlight the power of ABEL-FRET to probeGPCRs dynamics and offer valuable insights into GPCR conformational landscapes.

Note: The authors acknowledge Dr. Polina Khorn (Moscow Institute of Physicsand Technology, MIPT), who performed protein expression, labeling,purification, and nanodisc reconstitution under the supervision of Dr.AlekseyMishin and V.C. I.M. acknowledges BOF UHasselt (BOF21BL11)and funding from the European Union under the HORIZON TMA MSCAPostdoctoral Fellowships action (project MemProDx, 101149735). J.He.acknowledges the Research Foundation Flanders (FWO, grant numberG0B9922N). V.B. acknowledges DAAD Young Talents Programme LineA. M.B. gratefully acknowledges ABEL trap funding by the DeutscheForschungsgemeinschaft (DFG) through grants BO1891/10-2, BO1891/15-1, BO1891/16-1, BO1891/18-2. Additional support for the ABEL trapwas provided by an ACP Explore project within the ProExcellenceinitiative ACP2020 from the State of Thuringia to the Abbe Center ofPhotonics (Jena).

---

Contributing Institute(s):

1. Molekular- und Zellphysiologie (IBI-1)
2. Strukturbiochemie (IBI-7)

Research Program(s):

1. 5241 - Molecular Information Processing in Cellular Systems (POF4-524) (POF4-524)

Appears in the scientific report 2026

---

Database coverage:
; ; ; ; Article Processing Charges ; Clarivate Analytics Master Journal List ; Current Contents - Physical, Chemical and Earth Sciences ; DOAJ Seal ; Ebsco Academic Search ; Essential Science Indicators ; Fees ; IF >= 5 ; JCR ; PubMed Central ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection

---