"Ligand specific activation trajectories dictate GPCR signaling in cells" - by Thomas et al.[1] (Nature, Jan 14, 2026) is our featured scientific article for January.
G-protein coupled receptors (GPCRs) are among the most important signal switches in biology and major drug targets. For a long time, GPCR activation was viewed as a simple on / off process: a ligand binds, the receptor activates and signaling follows. Reality, however, is much more nuanced.
This study shows that different ligands activate the same GPCR through distinct activation trajectories – meaning the receptor passes through different intermediate states before reaching its active form. These early steps already determine how the receptor will signal inside the cell.
It’s not just whether a receptor is active. It’s about how it becomes active.
For years, scientists suspected already that different ligands could bias GPCR signaling. What was missing was direct evidence showing how this bias is encoded during activation.
The authors could demonstrate that:
Want to read more: access the full article here!
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[1] Thomas et al. (2026) Ligand specific activation trajectories dictate GPCR signaling in cells. Nature, https://doi.org/10.1038/s41586-025-09963-3
