Agonist efficacy at the β2AR is driven by the faster association rate of the Gs protein
The association rate (<i>k</i> <sub>on</sub>) of the G protein to the agonist β<sub>2</sub>AR complex is directly correlated with ligand efficacy. These data support a model in which higher-efficacy agonists induce the β<sub>2</sub>AR to adopt a conformation that is more likely to recruit G protein. Conversely, these data did not support the role of agonist binding kinetics in determining the molecular basis of efficacy.
Authors
- Clare R. Harwood (ORCID: https://orcid.org/0000-0003-1403-3666)
- Dmitry B. Veprintsev (ORCID: https://orcid.org/0000-0002-3583-5409)
- Eline J. Koers (ORCID: https://orcid.org/0000-0002-5352-9069)
- David A. Sykes (ORCID: https://orcid.org/0000-0002-6606-888X)
- Theo Redfern-Nichols (ORCID: https://orcid.org/0009-0000-7503-4510)
- Stephen J. Briddon (ORCID: https://orcid.org/0000-0001-8514-0827)
- Graham Ladds (ORCID: https://orcid.org/0000-0001-7320-9612)
- Colin Nicholson
- Owen Underwood
- Armin Nikpour Khoshgrudi
Institutions
- University of Nottingham (GB)
- University of Cambridge (GB)
- University of Birmingham (GB)
Publication Details
- Journal
- Frontiers in Pharmacology
- Published
- 2025-03-27
- DOI
- https://doi.org/10.3389/fphar.2025.1367991
- Citations
- 1
- Primary Topic
- Receptor Mechanisms and Signaling
- Type
- article
- Field-Weighted Citation Impact
- 0.81
Funders
- Royal Society
- Medical Research Council
- Biotechnology and Biological Sciences Research Council