- EMDB-31979: Neuropeptide Y Y1 Receptor (NPY1R) in Complex with G Protein and ... -
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Basic information
Entry
Database: EMDB / ID: EMD-31979
Title
Neuropeptide Y Y1 Receptor (NPY1R) in Complex with G Protein and its endogeneous Peptide-Agonist Neuropeptide Y (NPY)
Map data
Merged density of NPY-Y1R-Gi-scFv16 complex generated by vop maximum
Sample
Complex: Complex of Neuropeptide Y Y1 Receptor (NPY1R) with its endogeneous Peptide-Agonist Neuropeptide Y (NPY), G Protein and G-protein stabilizing antibody fragement (scFv16)
Complex: Neuropeptide Y Y1 Receptor (NPY1R)
Protein or peptide: Neuropeptide Y receptor type 1
Complex: nucleotide-free G-Protein heterotrimer
Protein or peptide: Guanine nucleotide-binding protein G(i) subunit alpha-1
Protein or peptide: Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1
Protein or peptide: Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2
Complex: Neuropeptide Y
Protein or peptide: Neuropeptide Y
Complex: single-chain antibody Fv fragment (scFv16)
Protein or peptide: single-chain antibody Fv fragment (scFv16)
Function / homology
Function and homology information
pancreatic polypeptide receptor activity / peptide YY receptor activity / neuropeptide Y receptor activity / synaptic signaling via neuropeptide / neuropeptide Y receptor binding / intestinal epithelial cell differentiation / positive regulation of appetite / neuropeptide receptor activity / adult feeding behavior / neuropeptide hormone activity ...pancreatic polypeptide receptor activity / peptide YY receptor activity / neuropeptide Y receptor activity / synaptic signaling via neuropeptide / neuropeptide Y receptor binding / intestinal epithelial cell differentiation / positive regulation of appetite / neuropeptide receptor activity / adult feeding behavior / neuropeptide hormone activity / neuropeptide binding / feeding behavior / central nervous system neuron development / outflow tract morphogenesis / neuronal dense core vesicle / G protein-coupled receptor signaling pathway, coupled to cyclic nucleotide second messenger / regulation of multicellular organism growth / calcium channel regulator activity / GABA-ergic synapse / Adenylate cyclase inhibitory pathway / neuropeptide signaling pathway / positive regulation of protein localization to cell cortex / regulation of cAMP-mediated signaling / FOXO-mediated transcription of oxidative stress, metabolic and neuronal genes / D2 dopamine receptor binding / G protein-coupled serotonin receptor binding / regulation of mitotic spindle organization / cellular response to forskolin / sensory perception of pain / adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway / Peptide ligand-binding receptors / locomotory behavior / 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 / 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 / cerebral cortex development / 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) / regulation of blood pressure / 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 / glucose metabolic process / GPER1 signaling / GDP binding / G-protein beta-subunit binding / Inactivation, recovery and regulation of the phototransduction cascade / heterotrimeric G-protein complex / neuron projection development / 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 / chemical synaptic transmission / cell population proliferation / Ras protein signal transduction / Extra-nuclear estrogen signaling / neuron projection / cell cycle / G protein-coupled receptor signaling pathway / cell division / lysosomal membrane Similarity search - Function
Neuropeptide Y1 receptor / Neuropeptide Y receptor family / Pancreatic hormone-like / Pancreatic hormone-like, conserved site / Pancreatic hormone peptide / Pancreatic hormone family signature. / Pancreatic hormone family profile. / Pancreatic hormones / neuropeptide F / peptide YY family / G-protein alpha subunit, group I / G-alpha domain profile. ...Neuropeptide Y1 receptor / Neuropeptide Y receptor family / Pancreatic hormone-like / Pancreatic hormone-like, conserved site / Pancreatic hormone peptide / Pancreatic hormone family signature. / Pancreatic hormone family profile. / Pancreatic hormones / neuropeptide F / peptide YY family / G-protein alpha subunit, group I / G-alpha domain profile. / Guanine nucleotide binding protein (G-protein), alpha subunit / G protein alpha subunit, helical insertion / G-protein alpha subunit / G protein alpha subunit / G-protein, gamma subunit / G-protein gamma subunit domain profile. / GGL domain / G-protein gamma-like domain superfamily / G-protein gamma-like domain / GGL domain / G protein gamma subunit-like motifs / Guanine nucleotide-binding protein, beta subunit / G-protein, beta subunit / G-protein coupled receptors family 1 signature. / G protein-coupled receptor, rhodopsin-like / GPCR, rhodopsin-like, 7TM / G-protein coupled receptors family 1 profile. / 7 transmembrane receptor (rhodopsin family) / G-protein beta WD-40 repeat / WD40 repeat, conserved site / Trp-Asp (WD) repeats signature. / Trp-Asp (WD) repeats profile. / Trp-Asp (WD) repeats circular profile. / WD domain, G-beta repeat / WD40 repeats / WD40 repeat / WD40-repeat-containing domain superfamily / WD40/YVTN repeat-like-containing domain superfamily / P-loop containing nucleoside triphosphate hydrolase Similarity search - Domain/homology
Pro-neuropeptide Y / Neuropeptide Y receptor type 1 / Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2 / Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1 / Guanine nucleotide-binding protein G(i) subunit alpha-1 Similarity search - Component
Biological species
Homo sapiens (human) / Mus musculus (house mouse)
Method
single particle reconstruction / cryo EM / Resolution: 3.2 Å
Journal: Nat Commun / Year: 2022 Title: Structural basis of neuropeptide Y signaling through Y1 receptor. Authors: Chaehee Park / Jinuk Kim / Seung-Bum Ko / Yeol Kyo Choi / Hyeongseop Jeong / Hyeonuk Woo / Hyunook Kang / Injin Bang / Sang Ah Kim / Tae-Young Yoon / Chaok Seok / Wonpil Im / Hee-Jung Choi / Abstract: Neuropeptide Y (NPY) is highly abundant in the brain and involved in various physiological processes related to food intake and anxiety, as well as human diseases such as obesity and cancer. However, ...Neuropeptide Y (NPY) is highly abundant in the brain and involved in various physiological processes related to food intake and anxiety, as well as human diseases such as obesity and cancer. However, the molecular details of the interactions between NPY and its receptors are poorly understood. Here, we report a cryo-electron microscopy structure of the NPY-bound neuropeptide Y1 receptor (YR) in complex with G protein. The NPY C-terminal segment forming the extended conformation binds deep into the YR transmembrane core, where the amidated C-terminal residue Y36 of NPY is located at the base of the ligand-binding pocket. Furthermore, the helical region and two N-terminal residues of NPY interact with YR extracellular loops, contributing to the high affinity of NPY for YR. The structural analysis of NPY-bound YR and mutagenesis studies provide molecular insights into the activation mechanism of YR upon NPY binding.
History
Deposition
Sep 19, 2021
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Header (metadata) release
Feb 23, 2022
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Map release
Feb 23, 2022
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Update
Feb 23, 2022
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Current status
Feb 23, 2022
Processing site: PDBj / Status: Released
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Structure visualization
Movie
Surface view with section colored by density value
Entire : Complex of Neuropeptide Y Y1 Receptor (NPY1R) with its endogeneou...
Entire
Name: Complex of Neuropeptide Y Y1 Receptor (NPY1R) with its endogeneous Peptide-Agonist Neuropeptide Y (NPY), G Protein and G-protein stabilizing antibody fragement (scFv16)
Components
Complex: Complex of Neuropeptide Y Y1 Receptor (NPY1R) with its endogeneous Peptide-Agonist Neuropeptide Y (NPY), G Protein and G-protein stabilizing antibody fragement (scFv16)
Complex: Neuropeptide Y Y1 Receptor (NPY1R)
Protein or peptide: Neuropeptide Y receptor type 1
Complex: nucleotide-free G-Protein heterotrimer
Protein or peptide: Guanine nucleotide-binding protein G(i) subunit alpha-1
Protein or peptide: Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1
Protein or peptide: Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2
Complex: Neuropeptide Y
Protein or peptide: Neuropeptide Y
Complex: single-chain antibody Fv fragment (scFv16)
Protein or peptide: single-chain antibody Fv fragment (scFv16)
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Supramolecule #1: Complex of Neuropeptide Y Y1 Receptor (NPY1R) with its endogeneou...
Supramolecule
Name: Complex of Neuropeptide Y Y1 Receptor (NPY1R) with its endogeneous Peptide-Agonist Neuropeptide Y (NPY), G Protein and G-protein stabilizing antibody fragement (scFv16) type: complex / ID: 1 / Parent: 0 / Macromolecule list: all
Molecular weight
Theoretical: 160 KDa
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Supramolecule #2: Neuropeptide Y Y1 Receptor (NPY1R)
Model: Quantifoil R1.2/1.3 / Material: COPPER / Mesh: 300 / Support film - Material: CARBON / Support film - topology: HOLEY / Support film - Film thickness: 11.0 nm / Pretreatment - Type: GLOW DISCHARGE / Pretreatment - Atmosphere: AIR
Vitrification
Cryogen name: ETHANE / Chamber humidity: 100 % / Chamber temperature: 285 K / Instrument: FEI VITROBOT MARK IV / Details: blot for 5 seconds before plunging.
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Electron microscopy
Microscope
FEI TITAN KRIOS
Specialist optics
Spherical aberration corrector: Microscope was modified with a Cs corrector
Image recording
Film or detector model: FEI FALCON III (4k x 4k) / Detector mode: COUNTING / Digitization - Dimensions - Width: 4096 pixel / Digitization - Dimensions - Height: 4096 pixel / Average electron dose: 40.0 e/Å2
Electron beam
Acceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN
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