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Title | Cryo-EM structure of the human MT-G signaling complex. |
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Journal, issue, pages | Nat Struct Mol Biol, Vol. 28, Issue 8, Page 694-701, Year 2021 |
Publish date | Aug 5, 2021 |
Authors | 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 / |
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 ...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. |
External links | Nat Struct Mol Biol / PubMed:34354246 |
Methods | EM (single particle) |
Resolution | 3.3 Å |
Structure data | EMDB-30627, PDB-7db6: |
Chemicals | ChemComp-JEV: |
Source |
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Keywords | SIGNALING PROTEIN / gpcr / g-protein / complex |