7VH0

MT2-remalteon-Gi complex

7VH0 の概要

• エントリーDOI: 10.2210/pdb7vh0/pdb
• EMDBエントリー: 31982
• 分子名称: Melatonin receptor type 1B, Guanine nucleotide-binding protein G(i) subunit alpha-1, Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1, ... (5 entities in total)
• 機能のキーワード: g protein coupled receptor, membrane protein
• 由来する生物種: Homo sapiens (human); 詳細
• タンパク質・核酸の鎖数: 5
• 化学式量合計: 189464.23

構造登録者

Wang, Q.G.,Lu, Q.Y. (登録日: 2021-09-20, 公開日: 2022-03-02, 最終更新日: 2025-07-02)

主引用文献

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

実験手法

ELECTRON MICROSCOPY (3.46 Å)