+Open data
-Basic information
Entry | Database: PDB / ID: 7db6 | ||||||
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Title | human melatonin receptor MT1 - Gi1 complex | ||||||
Components |
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Keywords | SIGNALING PROTEIN / gpcr / g-protein / complex | ||||||
Function / homology | Function and homology information melatonin receptor activity / organic cyclic compound binding / hormone binding / Class A/1 (Rhodopsin-like receptors) / Activation of G protein gated Potassium channels / G-protein activation / G beta:gamma signalling through PI3Kgamma / Prostacyclin signalling through prostacyclin receptor / Adrenaline,noradrenaline inhibits insulin secretion / G beta:gamma signalling through PLC beta ...melatonin receptor activity / organic cyclic compound binding / hormone binding / Class A/1 (Rhodopsin-like receptors) / Activation of G protein gated Potassium channels / G-protein activation / G beta:gamma signalling through PI3Kgamma / Prostacyclin signalling through prostacyclin receptor / Adrenaline,noradrenaline inhibits insulin secretion / G beta:gamma signalling through PLC beta / ADP signalling through P2Y purinoceptor 1 / Thromboxane signalling through TP receptor / Presynaptic function of Kainate receptors / G beta:gamma signalling through CDC42 / Inhibition of voltage gated Ca2+ channels via Gbeta/gamma subunits / Glucagon-type ligand receptors / G alpha (12/13) signalling events / G beta:gamma signalling through BTK / ADP signalling through P2Y purinoceptor 12 / Cooperation of PDCL (PhLP1) and TRiC/CCT in G-protein beta folding / mating behavior / Thrombin signalling through proteinase activated receptors (PARs) / Ca2+ pathway / Extra-nuclear estrogen signaling / G alpha (z) signalling events / G alpha (s) signalling events / G alpha (q) signalling events / G alpha (i) signalling events / Glucagon-like Peptide-1 (GLP1) regulates insulin secretion / Vasopressin regulates renal water homeostasis via Aquaporins / G protein-coupled receptor signaling pathway, coupled to cyclic nucleotide second messenger / Adenylate cyclase inhibitory pathway / positive regulation of protein localization to cell cortex / cell cortex region / regulation of cAMP-mediated signaling / D2 dopamine receptor binding / G protein-coupled serotonin receptor binding / regulation of mitotic spindle organization / cellular response to forskolin / adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway / Regulation of insulin secretion / G protein-coupled receptor binding / G protein-coupled receptor activity / G-protein beta/gamma-subunit complex binding / adenylate cyclase-modulating G protein-coupled receptor signaling pathway / ADP signalling through P2Y purinoceptor 12 / response to peptide hormone / Adrenaline,noradrenaline inhibits insulin secretion / G alpha (z) signalling events / cellular response to catecholamine stimulus / ADORA2B mediated anti-inflammatory cytokines production / adenylate cyclase-activating dopamine receptor signaling pathway / cellular response to prostaglandin E stimulus / circadian rhythm / GPER1 signaling / GDP binding / G-protein beta-subunit binding / heterotrimeric G-protein complex / cell cortex / G alpha (i) signalling events / midbody / G alpha (s) signalling events / Extra-nuclear estrogen signaling / receptor complex / cell cycle / G protein-coupled receptor signaling pathway / lysosomal membrane / cell division / GTPase activity / centrosome / GTP binding / nucleolus / magnesium ion binding / extracellular exosome / nucleoplasm / membrane / plasma membrane / cytoplasm Similarity search - Function | ||||||
Biological species | Homo sapiens (human) Rattus rattus (black rat) Bos taurus (cattle) Mus musculus (house mouse) | ||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.3 Å | ||||||
Authors | Okamoto, H.H. / Kusakizako, T. / Shihioya, W. / Yamashita, K. / Nishizawa, T. / Nureki, O. | ||||||
Citation | Journal: Nat Struct Mol Biol / Year: 2021 Title: Cryo-EM structure of the human MT-G signaling complex. Authors: Hiroyuki H Okamoto / Hirotake Miyauchi / Asuka Inoue / Francesco Raimondi / Hirokazu Tsujimoto / Tsukasa Kusakizako / Wataru Shihoya / Keitaro Yamashita / Ryoji Suno / Norimichi Nomura / ...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 / 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. | ||||||
History |
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-Structure visualization
Movie |
Movie viewer |
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Structure viewer | Molecule: MolmilJmol/JSmol |
-Downloads & links
-Download
PDBx/mmCIF format | 7db6.cif.gz | 207.1 KB | Display | PDBx/mmCIF format |
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PDB format | pdb7db6.ent.gz | 166 KB | Display | PDB format |
PDBx/mmJSON format | 7db6.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/db/7db6 ftp://data.pdbj.org/pub/pdb/validation_reports/db/7db6 | HTTPS FTP |
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-Related structure data
Related structure data | 30627MC M: map data used to model this data C: citing same article (ref.) |
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Similar structure data | |
EM raw data | EMPIAR-10714 (Title: human melatonin receptor MT1 - Gi1 complex / Data size: 878.0 Data #1: Unaligned movies for MT1-Gi complex [micrographs - multiframe]) |
-Links
-Assembly
Deposited unit |
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1 |
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-Components
-Guanine nucleotide-binding protein ... , 3 types, 3 molecules ABC
#1: Protein | Mass: 40415.031 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: GNAI1 / Production host: Spodoptera frugiperda (fall armyworm) / References: UniProt: P63096 |
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#2: Protein | Mass: 37799.270 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Rattus rattus (black rat) / Production host: Spodoptera frugiperda (fall armyworm) |
#3: Protein | Mass: 7547.685 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Bos taurus (cattle) / Gene: GNG2 / Production host: Spodoptera frugiperda (fall armyworm) / References: UniProt: P63212 |
-Antibody / Protein / Non-polymers , 3 types, 3 molecules ED
#4: Antibody | Mass: 27720.795 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Mus musculus (house mouse) / Production host: Spodoptera frugiperda (fall armyworm) |
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#5: Protein | Mass: 42222.805 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: MTNR1A / Production host: Homo sapiens (human) / References: UniProt: P48039 |
#6: Chemical | ChemComp-JEV / |
-Details
Has ligand of interest | Y |
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-Experimental details
-Experiment
Experiment | Method: ELECTRON MICROSCOPY |
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EM experiment | Aggregation state: PARTICLE / 3D reconstruction method: single particle reconstruction |
-Sample preparation
Component | Name: human melatonin receptor MT1 - Gi1 complex / Type: COMPLEX / Entity ID: #1-#5 / Source: MULTIPLE SOURCES |
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Source (natural) | Organism: Homo sapiens (human) |
Buffer solution | pH: 7.5 |
Specimen | Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES |
Vitrification | Instrument: FEI VITROBOT MARK IV / Cryogen name: ETHANE |
-Electron microscopy imaging
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |
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Microscopy | Model: FEI TITAN KRIOS |
Electron gun | Electron source: FIELD EMISSION GUN / Accelerating voltage: 300 kV / Illumination mode: FLOOD BEAM |
Electron lens | Mode: BRIGHT FIELDBright-field microscopy |
Image recording | Electron dose: 50 e/Å2 / Film or detector model: GATAN K3 BIOQUANTUM (6k x 4k) |
-Processing
Software | Name: PHENIX / Version: 1.14_3260: / Classification: refinement |
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CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION |
3D reconstruction | Resolution: 3.3 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 171412 / Symmetry type: POINT |