Happy to share our new preprint on the red-shifted channelrhodopsin ChR024, recently discovered by Inoue Lab (biorxiv.org/content/10.1...
), highlighting its long-wavelength absorption and ion conductance:
biorxiv.org/content/10.1...

Many thanks to our wonderful lab members and collaborators!

(3) Contrary to prior assumptions, 4‑CMTB, an FFA2‑specific ago‑PAM, binds the outer surface of TM6‑7, stabilizing it and shifting FFA2 equilibrium to its active state. Notably, although this pocket is unique to active FFA2, one mutation permits the activation of FFA3 by 4‑CMTB.

(2) The binding site of FFA2 antagonist, GLPG0974 has been controversial. Our data show that this compd binds just next to the ortho pocket, pushing the Tyr residue that separates the ortho and allosteric pockets and clashing with the ortho pocket; this Tyr residue acts as a micro‑lever switch.

(1) Wild‑type FFA2 is normally activated only by short‑chain fatty acids; however, when the ligand entry site is tuned, it can also be activated by long‑chain fatty acids!

We solved the cryo‑EM structures of (I) the active FFA2‑Gi complex with TUG‑1375 and 4‑CMTB, and (II) the inactive FFA2 in complex with GLPG0974. In combination with simulations and cell-based assays, we found several interesting things…, I’d like to highlight three key findings in this paper:

Happy to share our work on the ligand selectivity and allosteric regulation of FFA2 using a combination of cryo‑EM, MD simulations, and mol. pharmacology! It was a great collab. with Ishikita, Dror, and Inoue labs. Congrats to Mai, Kouki, Ryoji, and everyone involved! www.nature.com/articles/s41...

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