Structural basis and physiological significance of non-canonical Gs coupling to the prototypical Gi-coupled melatonin MT1 receptor
Atsuro Oishi, Hiroyuki H. Okamoto, Keisuke Ikegami, Ronan McHugh, Bernard Masri, Tsukasa Kusakizako, Kazuhiro Kobayashi, Angeliki Karamitri, Erika Cecon, Julie Dam, Miki Nagase, Irina G. Tikhonova, Osamu Nureki, Ralf Jockers
The paper shows MT1, a Gi-coupled receptor, can also couple to Gs proteins, activates the Gs/cAMP pathway under long-term melatonin exposure, and presents the first solved structure of a Gi-coupled receptor-Gs complex.
bioRxiv · Nov 8, 2025 · PreprintMolecular Biology