7DB6

human melatonin receptor MT1 - Gi1 complex

7DB6 の概要

• エントリーDOI: 10.2210/pdb7db6/pdb
• EMDBエントリー: 30627
• 分子名称: Guanine nucleotide-binding protein G(i) subunit alpha-1, Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1, Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2, ... (6 entities in total)
• 機能のキーワード: gpcr, g-protein, complex, signaling 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: 155964.93

構造登録者

Okamoto, H.H.,Kusakizako, T.,Shihioya, W.,Yamashita, K.,Nishizawa, T.,Nureki, O. (登録日: 2020-10-19, 公開日: 2021-08-18, 最終更新日: 2025-07-02)

主引用文献

Okamoto, H.H.,Miyauchi, H.,Inoue, A.,Raimondi, F.,Tsujimoto, H.,Kusakizako, T.,Shihoya, W.,Yamashita, K.,Suno, R.,Nomura, N.,Kobayashi, T.,Iwata, S.,Nishizawa, T.,Nureki, O.
Cryo-EM structure of the human MT 1 -G i signaling complex.
Nat.Struct.Mol.Biol., 28:694-701, 2021

PubMed Abstract: Melatonin receptors (MT and MT) transduce inhibitory signaling by melatonin (N-acetyl-5-methoxytryptamine), which is associated with sleep induction and circadian rhythm modulation. Although recently reported crystal structures of ligand-bound MT and MT elucidated the basis of ligand entry and recognition, the ligand-induced MT rearrangement leading to G-coupling remains unclear. Here we report a cryo-EM structure of the human MT-G signaling complex at 3.3 Å resolution, revealing melatonin-induced conformational changes propagated to the G-protein-coupling interface during activation. In contrast to other G-coupled receptors, MT exhibits a large outward movement of TM6, which is considered a specific feature of G-coupled receptors. Structural comparison of G and G complexes demonstrated conformational diversity of the C-terminal entry of the G protein, suggesting loose and variable interactions at the end of the α5 helix of G protein. These notions, together with our biochemical and computational analyses, highlight variable binding modes of Gα and provide the basis for the selectivity of G-protein signaling.

PubMed: 34354246
DOI: 10.1038/s41594-021-00634-1

実験手法

ELECTRON MICROSCOPY (3.3 Å)