- 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 / regulation of nerve growth factor production / peptide YY receptor activity / short-day photoperiodism / negative regulation of acute inflammatory response to antigenic stimulus / neuropeptide Y receptor activity / monocyte activation / positive regulation of dopamine metabolic process / positive regulation of nitric oxide metabolic process / positive regulation of appetite ...pancreatic polypeptide receptor activity / regulation of nerve growth factor production / peptide YY receptor activity / short-day photoperiodism / negative regulation of acute inflammatory response to antigenic stimulus / neuropeptide Y receptor activity / monocyte activation / positive regulation of dopamine metabolic process / positive regulation of nitric oxide metabolic process / positive regulation of appetite / neuropeptide Y receptor binding / intestinal epithelial cell differentiation / synaptic signaling via neuropeptide / positive regulation of eating behavior / adult feeding behavior / neuropeptide receptor activity / regulation of presynaptic cytosolic calcium ion concentration / neuropeptide hormone activity / neuropeptide binding / feeding behavior / positive regulation of cell-substrate adhesion / neuronal dense core vesicle / regulation of synaptic vesicle exocytosis / central nervous system neuron development / outflow tract morphogenesis / G protein-coupled receptor signaling pathway, coupled to cyclic nucleotide second messenger / regulation of multicellular organism growth / neuropeptide signaling pathway / FOXO-mediated transcription of oxidative stress, metabolic and neuronal genes / adenylate cyclase inhibitor activity / positive regulation of protein localization to cell cortex / T cell migration / Adenylate cyclase inhibitory pathway / D2 dopamine receptor binding / response to prostaglandin E / negative regulation of blood pressure / G protein-coupled serotonin receptor binding / adenylate cyclase regulator activity / adenylate cyclase-inhibiting serotonin receptor signaling pathway / sensory perception of pain / cellular response to forskolin / regulation of mitotic spindle organization / Peptide ligand-binding receptors / calcium channel regulator activity / Regulation of insulin secretion / locomotory behavior / positive regulation of cholesterol biosynthetic process / G protein-coupled receptor binding / negative regulation of insulin secretion / G protein-coupled receptor activity / adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway / cerebral cortex development / GABA-ergic synapse / response to peptide hormone / adenylate cyclase-modulating G protein-coupled receptor signaling pathway / regulation of blood pressure / centriolar satellite / G-protein beta/gamma-subunit complex binding / Olfactory Signaling Pathway / Activation of the phototransduction cascade / G beta:gamma signalling through PLC beta / Presynaptic function of Kainate receptors / Thromboxane signalling through TP receptor / G protein-coupled acetylcholine receptor signaling pathway / G-protein activation / Activation of G protein gated Potassium channels / Inhibition of voltage gated Ca2+ channels via Gbeta/gamma subunits / glucose metabolic process / terminal bouton / Prostacyclin signalling through prostacyclin receptor / G beta:gamma signalling through CDC42 / Glucagon signaling in metabolic regulation / G beta:gamma signalling through BTK / neuron projection development / Synthesis, secretion, and inactivation of Glucagon-like Peptide-1 (GLP-1) / ADP signalling through P2Y purinoceptor 12 / Sensory perception of sweet, bitter, and umami (glutamate) taste / photoreceptor disc membrane / Glucagon-type ligand receptors / Adrenaline,noradrenaline inhibits insulin secretion / Vasopressin regulates renal water homeostasis via Aquaporins / GDP binding / G alpha (z) signalling events / Glucagon-like Peptide-1 (GLP1) regulates insulin secretion / cellular response to catecholamine stimulus / ADP signalling through P2Y purinoceptor 1 / ADORA2B mediated anti-inflammatory cytokines production / G beta:gamma signalling through PI3Kgamma / Cooperation of PDCL (PhLP1) and TRiC/CCT in G-protein beta folding / adenylate cyclase-activating dopamine receptor signaling pathway / GPER1 signaling / Inactivation, recovery and regulation of the phototransduction cascade / cellular response to prostaglandin E stimulus / G-protein beta-subunit binding / heterotrimeric G-protein complex / G alpha (12/13) signalling events / sensory perception of taste / extracellular vesicle / signaling receptor complex adaptor activity / Thrombin signalling through proteinase activated receptors (PARs) 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 / Guanine nucleotide binding protein (G-protein), alpha subunit ...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 / Guanine nucleotide binding protein (G-protein), alpha subunit / G protein alpha subunit, helical insertion / G-protein alpha subunit / G-alpha domain profile. / G protein alpha subunit / G-protein, gamma subunit / G-protein gamma subunit domain profile. / G-protein gamma-like domain / G-protein gamma-like domain superfamily / GGL domain / G protein gamma subunit-like motifs / GGL domain / G protein beta WD-40 repeat protein / 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. / 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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