+Open data
-Basic information
Entry | Database: PDB / ID: 7vh0 | ||||||
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Title | MT2-remalteon-Gi complex | ||||||
Components |
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Keywords | MEMBRANE PROTEIN / G protein coupled receptor | ||||||
Function / homology | Function and homology information positive regulation of circadian sleep/wake cycle, non-REM sleep / melatonin receptor activity / regulation of neuronal action potential / negative regulation of transmission of nerve impulse / positive regulation of transmission of nerve impulse / Class A/1 (Rhodopsin-like receptors) / G-protein activation / Activation of the phototransduction cascade / Glucagon-type ligand receptors / Thromboxane signalling through TP receptor ...positive regulation of circadian sleep/wake cycle, non-REM sleep / melatonin receptor activity / regulation of neuronal action potential / negative regulation of transmission of nerve impulse / positive regulation of transmission of nerve impulse / Class A/1 (Rhodopsin-like receptors) / G-protein activation / Activation of the phototransduction cascade / Glucagon-type ligand receptors / Thromboxane signalling through TP receptor / Sensory perception of sweet, bitter, and umami (glutamate) taste / G beta:gamma signalling through PI3Kgamma / G beta:gamma signalling through CDC42 / Ca2+ pathway / Cooperation of PDCL (PhLP1) and TRiC/CCT in G-protein beta folding / Activation of G protein gated Potassium channels / Inhibition of voltage gated Ca2+ channels via Gbeta/gamma subunits / camera-type eye development / G alpha (z) signalling events / Vasopressin regulates renal water homeostasis via Aquaporins / Glucagon-like Peptide-1 (GLP1) regulates insulin secretion / Adrenaline,noradrenaline inhibits insulin secretion / ADP signalling through P2Y purinoceptor 12 / G alpha (q) signalling events / Thrombin signalling through proteinase activated receptors (PARs) / G alpha (i) signalling events / alkylglycerophosphoethanolamine phosphodiesterase activity / negative regulation of vasoconstriction / photoreceptor outer segment membrane / spectrin binding / negative regulation of cGMP-mediated signaling / negative regulation of cytosolic calcium ion concentration / regulation of insulin secretion / G protein-coupled receptor signaling pathway, coupled to cyclic nucleotide second messenger / photoreceptor outer segment / T cell migration / Adenylate cyclase inhibitory pathway / positive regulation of protein localization to cell cortex / negative regulation of insulin secretion / regulation of cAMP-mediated signaling / D2 dopamine receptor binding / G protein-coupled serotonin receptor binding / regulation of mitotic spindle organization / cardiac muscle cell apoptotic process / cellular response to forskolin / photoreceptor inner segment / adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway / G-protein beta/gamma-subunit complex binding / Regulation of insulin secretion / G protein-coupled receptor binding / G protein-coupled receptor activity / adenylate cyclase-modulating G protein-coupled receptor signaling pathway / response to peptide hormone / ADP signalling through P2Y purinoceptor 12 / G alpha (z) signalling events / Adrenaline,noradrenaline inhibits insulin secretion / ADORA2B mediated anti-inflammatory cytokines production / sensory perception of taste / GPER1 signaling / GDP binding / heterotrimeric G-protein complex / Hydrolases; Acting on acid anhydrides; Acting on GTP to facilitate cellular and subcellular movement / signaling receptor complex adaptor activity / GTPase binding / glucose homeostasis / retina development in camera-type eye / phospholipase C-activating G protein-coupled receptor signaling pathway / positive regulation of cytosolic calcium ion concentration / cell cortex / midbody / G alpha (i) signalling events / cellular response to hypoxia / cell body / G alpha (s) signalling events / chemical synaptic transmission / negative regulation of neuron apoptotic process / cell population proliferation / Extra-nuclear estrogen signaling / G protein-coupled receptor signaling pathway / lysosomal membrane / cell division / GTPase activity / centrosome / dendrite / synapse / GTP binding / protein-containing complex binding / nucleolus / magnesium ion binding / extracellular exosome / nucleoplasm / plasma membrane / cytoplasm Similarity search - Function | ||||||
Biological species | Homo sapiens (human) Rattus norvegicus (Norway rat) | ||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.46 Å | ||||||
Authors | Wang, Q.G. / Lu, Q.Y. | ||||||
Funding support | China, 1items
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Citation | Journal: Nat Commun / Year: 2022 Title: Structural basis of the ligand binding and signaling mechanism of melatonin receptors. Authors: Qinggong Wang / Qiuyuan Lu / Qiong Guo / Maikun Teng / Qingguo Gong / Xu Li / Yang Du / Zheng Liu / Yuyong Tao / Abstract: Melatonin receptors (MT and MT in humans) are family A G protein-coupled receptors that respond to the neurohormone melatonin to regulate circadian rhythm and sleep. Numerous efforts have been made ...Melatonin receptors (MT and MT in humans) are family A G protein-coupled receptors that respond to the neurohormone melatonin to regulate circadian rhythm and sleep. Numerous efforts have been made to develop drugs targeting melatonin receptors for the treatment of insomnia, circadian rhythm disorder, and cancer. However, designing subtype-selective melatonergic drugs remains challenging. Here, we report the cryo-EM structures of the MT-G signaling complex with 2-iodomelatonin and ramelteon and the MT-G signaling complex with ramelteon. These structures, together with the reported functional data, reveal that although MT and MT possess highly similar orthosteric ligand-binding pockets, they also display distinctive features that could be targeted to design subtype-selective drugs. The unique structural motifs in MT and MT mediate structural rearrangements with a particularly wide opening on the cytoplasmic side. G is engaged in the receptor core shared by MT and MT and presents a conformation deviating from those in other G complexes. Together, our results provide new clues for designing melatonergic drugs and further insights into understanding the G protein coupling mechanism. | ||||||
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 | 7vh0.cif.gz | 211.1 KB | Display | PDBx/mmCIF format |
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PDB format | pdb7vh0.ent.gz | 163.6 KB | Display | PDB format |
PDBx/mmJSON format | 7vh0.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 7vh0_validation.pdf.gz | 897.4 KB | Display | wwPDB validaton report |
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Full document | 7vh0_full_validation.pdf.gz | 911.1 KB | Display | |
Data in XML | 7vh0_validation.xml.gz | 35.8 KB | Display | |
Data in CIF | 7vh0_validation.cif.gz | 54.4 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/vh/7vh0 ftp://data.pdbj.org/pub/pdb/validation_reports/vh/7vh0 | HTTPS FTP |
-Related structure data
Related structure data | 31982MC 7vgyC 7vgzC M: map data used to model this data C: citing same article (ref.) |
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Similar structure data |
-Links
-Assembly
Deposited unit |
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1 |
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-Components
#1: Protein | Mass: 40308.285 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: MTNR1B / Production host: Spodoptera frugiperda (fall armyworm) / References: UniProt: P49286 | ||||
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#2: Protein | Mass: 40340.887 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 | ||||
#3: Protein | Mass: 39021.648 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Rattus norvegicus (Norway rat) / Gene: Gnb1 / Production host: Spodoptera frugiperda (fall armyworm) / References: UniProt: P54311 | ||||
#4: Antibody | Mass: 34767.035 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: MTNR1B / Production host: Spodoptera frugiperda (fall armyworm) #5: Chemical | ChemComp-JEV / | Has ligand of interest | N | |
-Experimental details
-Experiment
Experiment | Method: ELECTRON MICROSCOPY |
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EM experiment | Aggregation state: 2D ARRAY / 3D reconstruction method: single particle reconstruction |
-Sample preparation
Component | Name: melatonin receptor 2 with G peotein complex / Type: COMPLEX / Entity ID: #1-#4 / Source: MULTIPLE SOURCES |
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Source (natural) | Organism: Homo sapiens (human) |
Buffer solution | pH: 7.4 |
Specimen | Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES |
Vitrification | Cryogen name: OTHER |
-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 FIELD / Nominal defocus max: 2000 nm / Nominal defocus min: 1200 nm |
Image recording | Electron dose: 70 e/Å2 / Film or detector model: GATAN K3 (6k x 4k) |
-Processing
Software | Name: PHENIX / Version: 1.19.2_4158: / Classification: refinement | ||||||||||||||||||||||||
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CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION | ||||||||||||||||||||||||
3D reconstruction | Resolution: 3.46 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 335170 / Symmetry type: POINT | ||||||||||||||||||||||||
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