Cryo-EM structure of the human MT1–Gi signaling complex

Hiroyuki H. Okamoto, Hirotake Miyauchi, Asuka Inoue, Francesco Raimondi, Hirokazu Tsujimoto, Tsukasa Kusakizako, Wataru Shihoya, Keitaro Yamashita, Ryoji Suno, Norimichi Nomura, Takuya Kobayashi, So Iwata, Tomohiro Nishizawa, Osamu Nureki

研究成果: Article査読

1 被引用数 (Scopus)

抄録

Melatonin receptors (MT1 and MT2) 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 MT1 and MT2 elucidated the basis of ligand entry and recognition, the ligand-induced MT1 rearrangement leading to Gi-coupling remains unclear. Here we report a cryo-EM structure of the human MT1–Gi 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 Gi-coupled receptors, MT1 exhibits a large outward movement of TM6, which is considered a specific feature of Gs-coupled receptors. Structural comparison of Gi and Gs complexes demonstrated conformational diversity of the C-terminal entry of the Gi protein, suggesting loose and variable interactions at the end of the α5 helix of Gi protein. These notions, together with our biochemical and computational analyses, highlight variable binding modes of Gαi and provide the basis for the selectivity of G-protein signaling.

本文言語English
ページ(範囲)694-701
ページ数8
ジャーナルNature Structural and Molecular Biology
28
8
DOI
出版ステータスPublished - 2021 8

ASJC Scopus subject areas

  • 構造生物学
  • 分子生物学

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