7VGY

Melatonin receptor1-2-Iodomelatonin-Gicomplex

Summary for 7VGY

• Entry DOI: 10.2210/pdb7vgy/pdb
• EMDB information: 31980
• Descriptor: Melatonin receptor type 1A, Guanine nucleotide-binding protein G(i) subunit alpha-1, Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1, ... (7 entities in total)
• Functional Keywords: g protein coupled receptor, membrane protein
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 5
• Total formula weight: 152938.45

Authors

Wang, Q.G.,Lu, Q.Y. (deposition date: 2021-09-20, release date: 2022-03-02, Last modification date: 2024-11-06)

Primary citation

Wang, Q.,Lu, Q.,Guo, Q.,Teng, M.,Gong, Q.,Li, X.,Du, Y.,Liu, Z.,Tao, Y.
Structural basis of the ligand binding and signaling mechanism of melatonin receptors.
Nat Commun, 13:454-454, 2022

PubMed Abstract: Melatonin receptors (MT and MT 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 MT-G signaling complex with 2-iodomelatonin and ramelteon and the MT-G signaling complex with ramelteon. These structures, together with the reported functional data, reveal that although MT and MT possess highly similar orthosteric ligand-binding pockets, they also display distinctive features that could be targeted to design subtype-selective drugs. The unique structural motifs in MT and MT mediate structural rearrangements with a particularly wide opening on the cytoplasmic side. G is engaged in the receptor core shared by MT and MT and presents a conformation deviating from those in other G complexes. Together, our results provide new clues for designing melatonergic drugs and further insights into understanding the G protein coupling mechanism.

PubMed: 35075127
DOI: 10.1038/s41467-022-28111-3

Experimental method

ELECTRON MICROSCOPY (3.1 Å)