7DB6

human melatonin receptor MT1 - Gi1 complex

Summary for 7DB6

• Entry DOI: 10.2210/pdb7db6/pdb
• EMDB information: 30627
• Descriptor: 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)
• Functional Keywords: gpcr, g-protein, complex, signaling protein
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 5
• Total formula weight: 155964.93

Authors

Okamoto, H.H.,Kusakizako, T.,Shihioya, W.,Yamashita, K.,Nishizawa, T.,Nureki, O. (deposition date: 2020-10-19, release date: 2021-08-18, Last modification date: 2025-07-02)

Primary citation

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

Experimental method

ELECTRON MICROSCOPY (3.3 Å)