Structural basis of the ligand binding and signaling mechanism of melatonin receptors.

ABSTRACT: Melatonin receptors (MT₁ and MT₂ in humans) are family A G protein-coupled receptors that respond to the neurohormone melatonin to regulate circadian rhythm and sleep. Numerous efforts have been made to develop drugs targeting melatonin receptors for the treatment of insomnia, circadian rhythm disorder, and cancer. However, designing subtype-selective melatonergic drugs remains challenging. Here, we report the cryo-EM structures of the MT₁-G_i signaling complex with 2-iodomelatonin and ramelteon and the MT₂-G_i signaling complex with ramelteon. These structures, together with the reported functional data, reveal that although MT₁ and MT₂ possess highly similar orthosteric ligand-binding pockets, they also

SUBMITTER: Wang Q 

PROVIDER: S-EPMC8786939 | biostudies-literature | 2022 Jan

REPOSITORIES: biostudies-literature