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- EMDB-33984: Complex structure of Neuropeptide Y Y2 receptor in complex with P... -
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Basic information
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Title | Complex structure of Neuropeptide Y Y2 receptor in complex with PYY(3-36) and Gi | |||||||||
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Function / homology | ![]() negative regulation of nervous system process / peptide YY receptor activity / positive regulation of circadian sleep/wake cycle, non-REM sleep / positive regulation of peptide secretion / neuropeptide Y receptor activity / neuropeptide Y receptor binding / intestinal epithelial cell differentiation / synaptic signaling via neuropeptide / negative regulation of secretion / cardiac left ventricle morphogenesis ...negative regulation of nervous system process / peptide YY receptor activity / positive regulation of circadian sleep/wake cycle, non-REM sleep / positive regulation of peptide secretion / neuropeptide Y receptor activity / neuropeptide Y receptor binding / intestinal epithelial cell differentiation / synaptic signaling via neuropeptide / negative regulation of secretion / cardiac left ventricle morphogenesis / positive regulation of smooth muscle contraction / positive regulation of dopamine secretion / negative regulation of excitatory postsynaptic potential / neuropeptide hormone activity / feeding behavior / negative regulation of synaptic transmission, glutamatergic / non-motile cilium / negative regulation of cAMP/PKA signal transduction / positive regulation of cell-substrate adhesion / negative regulation of feeding behavior / outflow tract morphogenesis / nitric oxide mediated signal transduction / neuropeptide signaling pathway / behavioral fear response / 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 / G protein-coupled serotonin receptor binding / adenylate cyclase regulator activity / adenylate cyclase-inhibiting serotonin receptor signaling pathway / 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 / adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway / hormone activity / response to peptide hormone / adenylate cyclase-modulating G protein-coupled receptor signaling pathway / 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 / Prostacyclin signalling through prostacyclin receptor / G beta:gamma signalling through CDC42 / Glucagon signaling in metabolic regulation / G beta:gamma signalling through BTK / 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 activity / signaling receptor complex adaptor activity / presynapse / Thrombin signalling through proteinase activated receptors (PARs) / retina development in camera-type eye / G protein activity / positive regulation of cytosolic calcium ion concentration / GTPase binding / Ca2+ pathway / midbody / fibroblast proliferation / High laminar flow shear stress activates signaling by PIEZO1 and PECAM1:CDH5:KDR in endothelial cells / cell cortex / G alpha (i) signalling events / G alpha (s) signalling events Similarity search - Function | |||||||||
Biological species | ![]() ![]() ![]() | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 2.95 Å | |||||||||
![]() | Kang H / Park C / Kim J / Choi H-J | |||||||||
Funding support | ![]()
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![]() | ![]() Title: Structural basis for Y2 receptor-mediated neuropeptide Y and peptide YY signaling. Authors: Hyunook Kang / Chaehee Park / Yeol Kyo Choi / Jungnam Bae / Sohee Kwon / Jinuk Kim / Chulwon Choi / Chaok Seok / Wonpil Im / Hee-Jung Choi / ![]() ![]() Abstract: Neuropeptide Y (NPY) and its receptors are expressed in various human tissues including the brain where they regulate appetite and emotion. Upon NPY stimulation, the neuropeptide Y1 and Y2 receptors ...Neuropeptide Y (NPY) and its receptors are expressed in various human tissues including the brain where they regulate appetite and emotion. Upon NPY stimulation, the neuropeptide Y1 and Y2 receptors (YR and YR, respectively) activate G signaling, but their physiological responses to food intake are different. In addition, deletion of the two N-terminal amino acids of peptide YY (PYY(3-36)), the endogenous form found in circulation, can stimulate YR but not YR, suggesting that YR and YR may have distinct ligand-binding modes. Here, we report the cryo-electron microscopy structures of the PYY(3-36)‒YR‒G and NPY‒YR‒G complexes. Using cell-based assays, molecular dynamics simulations, and structural analysis, we revealed the molecular basis of the exclusive binding of PYY(3-36) to YR. Furthermore, we demonstrated that YR favors G protein signaling over β-arrestin signaling upon activation, whereas YR does not show a preference between these two pathways. | |||||||||
History |
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Structure visualization
Supplemental images |
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Downloads & links
-EMDB archive
Map data | ![]() | 228.8 MB | ![]() | |
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Header (meta data) | ![]() ![]() | 26.1 KB 26.1 KB | Display Display | ![]() |
Images | ![]() | 88.1 KB | ||
Others | ![]() ![]() | 230 MB 230.1 MB | ||
Archive directory | ![]() ![]() | HTTPS FTP |
-Validation report
Summary document | ![]() | 420.3 KB | Display | ![]() |
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Full document | ![]() | 419.9 KB | Display | |
Data in XML | ![]() | 7 KB | Display | |
Data in CIF | ![]() | 8 KB | Display | |
Arichive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 7yonMC ![]() 7yooC C: citing same article ( M: atomic model generated by this map |
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Similar structure data | Similarity search - Function & homology ![]() |
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Links
EMDB pages | ![]() ![]() |
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Related items in Molecule of the Month |
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Map
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Annotation | Composite map | ||||||||||||||||||||||||||||||||||||
Projections & slices | Image control
Images are generated by Spider. | ||||||||||||||||||||||||||||||||||||
Voxel size | X=Y=Z: 0.849 Å | ||||||||||||||||||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||
Details | EMDB XML:
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-Supplemental data
-Additional map: Local refined map of G-protein complex
File | emd_33984_additional_1.map | ||||||||||||
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Annotation | Local refined map of G-protein complex | ||||||||||||
Projections & Slices |
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Density Histograms |
-Additional map: Local refined map of PYY(3-36)-Y2R
File | emd_33984_additional_2.map | ||||||||||||
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Annotation | Local refined map of PYY(3-36)-Y2R | ||||||||||||
Projections & Slices |
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Density Histograms |
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Sample components
+Entire : Complex structure of PYY(3-36)-Y2R-Gi-scFv16
+Supramolecule #1: Complex structure of PYY(3-36)-Y2R-Gi-scFv16
+Supramolecule #2: Guanine nucleotide-binding protein
+Supramolecule #3: scFv16
+Supramolecule #4: PYY(3-36)
+Macromolecule #1: Guanine nucleotide-binding protein G(i) subunit alpha-1
+Macromolecule #2: Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1
+Macromolecule #3: Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2
+Macromolecule #4: Peptide YY(3-36)
+Macromolecule #5: Neuropeptide Y receptor type 2
+Macromolecule #6: single-chain antibody Fv fragment (scFv16)
+Macromolecule #7: water
-Experimental details
-Structure determination
Method | cryo EM |
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![]() | single particle reconstruction |
Aggregation state | particle |
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Sample preparation
Concentration | 10 mg/mL |
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Buffer | pH: 7.5 |
Grid | Model: Quantifoil R1.2/1.3 / Material: COPPER / Mesh: 200 / Pretreatment - Type: GLOW DISCHARGE |
Vitrification | Cryogen name: ETHANE / Chamber humidity: 100 % / Chamber temperature: 278 K / Instrument: FEI VITROBOT MARK IV |
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Electron microscopy
Microscope | FEI TITAN KRIOS |
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Specialist optics | Energy filter - Name: GIF Bioquantum / Energy filter - Slit width: 20 eV |
Image recording | Film or detector model: GATAN K3 BIOQUANTUM (6k x 4k) / Average electron dose: 60.5 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: ![]() |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Nominal defocus max: 2.0 µm / Nominal defocus min: 0.75 µm |
Sample stage | Cooling holder cryogen: NITROGEN |
Experimental equipment | ![]() Model: Titan Krios / Image courtesy: FEI Company |