[English] 日本語
Yorodumi- PDB-7x9c: Cryo-EM structure of neuropeptide Y Y4 receptor in complex with P... -
+Open data
-Basic information
Entry | Database: PDB / ID: 7x9c | ||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Title | Cryo-EM structure of neuropeptide Y Y4 receptor in complex with PP and Gi | ||||||||||||
Components |
| ||||||||||||
Keywords | SIGNALING PROTEIN / pancreatic polypeptide / Gi protein | ||||||||||||
Function / homology | Function and homology information pancreatic polypeptide receptor activity / neuropeptide Y receptor binding / neuropeptide hormone activity / feeding behavior / plasma membrane => GO:0005886 / peptide hormone binding / protein secretion / Adenylate cyclase inhibitory pathway / neuropeptide signaling pathway / positive regulation of protein localization to cell cortex ...pancreatic polypeptide receptor activity / neuropeptide Y receptor binding / neuropeptide hormone activity / feeding behavior / plasma membrane => GO:0005886 / peptide hormone binding / protein secretion / Adenylate cyclase inhibitory pathway / neuropeptide signaling pathway / positive regulation of protein localization to cell cortex / 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 / Peptide ligand-binding receptors / Regulation of insulin secretion / G protein-coupled receptor binding / G protein-coupled receptor activity / G-protein beta/gamma-subunit complex binding / Olfactory Signaling Pathway / Activation of the phototransduction cascade / adenylate cyclase-modulating G protein-coupled receptor signaling pathway / G beta:gamma signalling through PLC beta / Presynaptic function of Kainate receptors / Thromboxane signalling through TP receptor / G-protein activation / hormone activity / G protein-coupled acetylcholine receptor signaling pathway / Activation of G protein gated Potassium channels / Inhibition of voltage gated Ca2+ channels via Gbeta/gamma subunits / Prostacyclin signalling through prostacyclin receptor / Glucagon signaling in metabolic regulation / G beta:gamma signalling through CDC42 / ADP signalling through P2Y purinoceptor 12 / G beta:gamma signalling through BTK / response to peptide hormone / Synthesis, secretion, and inactivation of Glucagon-like Peptide-1 (GLP-1) / Sensory perception of sweet, bitter, and umami (glutamate) taste / photoreceptor disc membrane / Adrenaline,noradrenaline inhibits insulin secretion / Glucagon-type ligand receptors / Vasopressin regulates renal water homeostasis via Aquaporins / G alpha (z) signalling events / cellular response to catecholamine stimulus / Glucagon-like Peptide-1 (GLP1) regulates insulin secretion / ADORA2B mediated anti-inflammatory cytokines production / sensory perception of taste / ADP signalling through P2Y purinoceptor 1 / adenylate cyclase-activating dopamine receptor signaling pathway / G beta:gamma signalling through PI3Kgamma / cellular response to prostaglandin E stimulus / Cooperation of PDCL (PhLP1) and TRiC/CCT in G-protein beta folding / GPER1 signaling / GDP binding / G-protein beta-subunit binding / Inactivation, recovery and regulation of the phototransduction cascade / heterotrimeric G-protein complex / G alpha (12/13) signalling events / extracellular vesicle / signaling receptor complex adaptor activity / Thrombin signalling through proteinase activated receptors (PARs) / GTPase binding / retina development in camera-type eye / phospholipase C-activating G protein-coupled receptor signaling pathway / Ca2+ pathway / cell cortex / midbody / G alpha (i) signalling events / fibroblast proliferation / G alpha (s) signalling events / G alpha (q) signalling events / cell population proliferation / Ras protein signal transduction / Extra-nuclear estrogen signaling / cell cycle / G protein-coupled receptor signaling pathway / cell division / lysosomal membrane / GTPase activity / centrosome / synapse / protein-containing complex binding / nucleolus / GTP binding / magnesium ion binding / signal transduction / extracellular space / extracellular exosome / extracellular region / nucleoplasm / membrane / plasma membrane / cytoplasm / cytosol Similarity search - Function | ||||||||||||
Biological species | Homo sapiens (human) | ||||||||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3 Å | ||||||||||||
Authors | Tang, T. / Han, S. / Zhao, Q. / Wu, B. | ||||||||||||
Funding support | China, 3items
| ||||||||||||
Citation | Journal: Sci Adv / Year: 2022 Title: Receptor-specific recognition of NPY peptides revealed by structures of NPY receptors. Authors: Tingting Tang / Qiuxiang Tan / Shuo Han / Anne Diemar / Kristin Löbner / Hongyu Wang / Corinna Schüß / Victoria Behr / Karin Mörl / Mu Wang / Xiaojing Chu / Cuiying Yi / Max Keller / ...Authors: Tingting Tang / Qiuxiang Tan / Shuo Han / Anne Diemar / Kristin Löbner / Hongyu Wang / Corinna Schüß / Victoria Behr / Karin Mörl / Mu Wang / Xiaojing Chu / Cuiying Yi / Max Keller / Jacob Kofoed / Steffen Reedtz-Runge / Anette Kaiser / Annette G Beck-Sickinger / Qiang Zhao / Beili Wu / Abstract: In response to three highly conserved neuropeptides, neuropeptide Y (NPY), peptide YY, and pancreatic polypeptide (PP), four G protein-coupled receptors mediate multiple essential physiological ...In response to three highly conserved neuropeptides, neuropeptide Y (NPY), peptide YY, and pancreatic polypeptide (PP), four G protein-coupled receptors mediate multiple essential physiological processes, such as food intake, vasoconstriction, sedation, and memory retention. Here, we report the structures of the human Y, Y, and Y receptors in complex with NPY or PP, and the G protein. These structures reveal distinct binding poses of the peptide upon coupling to different receptors, reflecting the importance of the conformational plasticity of the peptide in recognizing the NPY receptors. The N terminus of the peptide forms extensive interactions with the Y receptor, but not with the Y and Y receptors. Supported by mutagenesis and functional studies, subtype-specific interactions between the receptors and peptides were further observed. These findings provide insight into key factors that govern NPY signal recognition and transduction, and would enable development of selective drugs. | ||||||||||||
History |
|
-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
---|
-Downloads & links
-Download
PDBx/mmCIF format | 7x9c.cif.gz | 178.8 KB | Display | PDBx/mmCIF format |
---|---|---|---|---|
PDB format | pdb7x9c.ent.gz | 139.2 KB | Display | PDB format |
PDBx/mmJSON format | 7x9c.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 7x9c_validation.pdf.gz | 796.6 KB | Display | wwPDB validaton report |
---|---|---|---|---|
Full document | 7x9c_full_validation.pdf.gz | 805.6 KB | Display | |
Data in XML | 7x9c_validation.xml.gz | 31.4 KB | Display | |
Data in CIF | 7x9c_validation.cif.gz | 46.1 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/x9/7x9c ftp://data.pdbj.org/pub/pdb/validation_reports/x9/7x9c | HTTPS FTP |
-Related structure data
Related structure data | 33071MC 7x9aC 7x9bC M: map data used to model this data C: citing same article (ref.) |
---|---|
Similar structure data | Similarity search - Function & homologyF&H Search |
-Links
-Assembly
Deposited unit |
|
---|---|
1 |
|
-Components
#1: Protein | Mass: 42755.215 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: NPY4R, PPYR1 / Production host: Trichoplusia ni (cabbage looper) / References: UniProt: P50391 |
---|---|
#2: Protein | Mass: 40447.141 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: GNAI1 / Production host: Trichoplusia ni (cabbage looper) / References: UniProt: P63096 |
#3: Protein | Mass: 38744.371 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: GNB1 / Production host: Trichoplusia ni (cabbage looper) / References: UniProt: P62873 |
#4: Protein | Mass: 7861.143 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: GNG2 / Production host: Trichoplusia ni (cabbage looper) / References: UniProt: P59768 |
#5: Protein/peptide | Mass: 4185.743 Da / Num. of mol.: 1 / Source method: obtained synthetically / Source: (synth.) Homo sapiens (human) / References: UniProt: P01298 |
Has ligand of interest | N |
-Experimental details
-Experiment
Experiment | Method: ELECTRON MICROSCOPY |
---|---|
EM experiment | Aggregation state: PARTICLE / 3D reconstruction method: single particle reconstruction |
-Sample preparation
Component |
| ||||||||||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Source (natural) | Organism: Homo sapiens (human) | ||||||||||||||||||||||||
Source (recombinant) | Organism: Trichoplusia ni (cabbage looper) | ||||||||||||||||||||||||
Buffer solution | pH: 7.5 | ||||||||||||||||||||||||
Specimen | Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES | ||||||||||||||||||||||||
Vitrification | Cryogen name: ETHANE |
-Electron microscopy imaging
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |
---|---|
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: 1500 nm / Nominal defocus min: 800 nm |
Image recording | Electron dose: 70 e/Å2 / Film or detector model: GATAN K3 BIOQUANTUM (6k x 4k) |
-Processing
Software |
| ||||||||||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
CTF correction | Type: NONE | ||||||||||||||||||||||||
3D reconstruction | Resolution: 3 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 1047385 / Symmetry type: POINT | ||||||||||||||||||||||||
Refinement | Cross valid method: NONE Stereochemistry target values: GeoStd + Monomer Library + CDL v1.2 | ||||||||||||||||||||||||
Displacement parameters | Biso mean: 67.23 Å2 | ||||||||||||||||||||||||
Refine LS restraints |
|