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Open data
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Basic information
Entry | Database: PDB / ID: 8k6m | |||||||||||||||||||||||||||||||||||||||||||||
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Title | Structural complex of neuropeptide Y receptor 1 | |||||||||||||||||||||||||||||||||||||||||||||
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![]() | MEMBRANE PROTEIN / neuropeptide Y receptor 1 / complex | |||||||||||||||||||||||||||||||||||||||||||||
Function / homology | ![]() 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 / negative regulation of adenylate cyclase-activating adrenergic receptor signaling pathway / adult feeding behavior / neuropeptide receptor activity / negative regulation of calcium ion-dependent exocytosis / regulation of presynaptic cytosolic calcium ion concentration / G protein-coupled adenosine receptor signaling pathway / negative regulation of adenylate cyclase activity / positive regulation of urine volume / neuropeptide hormone activity / positive regulation of neural precursor cell proliferation / negative regulation of synaptic transmission / neuropeptide binding / feeding behavior / positive regulation of cell-substrate adhesion / gamma-aminobutyric acid signaling pathway / neuronal dense core vesicle / central nervous system neuron development / regulation of synaptic vesicle exocytosis / outflow tract morphogenesis / regulation of calcium ion transport / negative regulation of apoptotic signaling pathway / 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 inhibitory pathway / positive regulation of vascular associated smooth muscle cell proliferation / negative regulation of blood pressure / sensory perception of pain / response to nutrient / calcium channel regulator activity / Peptide ligand-binding receptors / hippocampal mossy fiber to CA3 synapse / positive regulation of superoxide anion generation / locomotory behavior / Regulation of insulin secretion / G protein-coupled receptor binding / G protein-coupled receptor activity / adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway / cerebral cortex development / GABA-ergic synapse / regulation of blood pressure / 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 / terminal bouton / 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 / adenylate cyclase-activating G protein-coupled receptor signaling pathway / glucose metabolic process / 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) / neuron projection development / 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 / 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) / retina development in camera-type eye Similarity search - Function | |||||||||||||||||||||||||||||||||||||||||||||
Biological species | ![]() ![]() ![]() | |||||||||||||||||||||||||||||||||||||||||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.3 Å | |||||||||||||||||||||||||||||||||||||||||||||
![]() | Shen, S.Y. / Zhao, C. / Shao, Z.H. | |||||||||||||||||||||||||||||||||||||||||||||
Funding support | ![]()
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![]() | ![]() Title: Structural basis of neuropeptide Y signaling through Y and Y receptors. Authors: Siyuan Shen / Yue Deng / Chenglong Shen / Haidi Chen / Lin Cheng / Chao Wu / Chang Zhao / Zhiqian Yang / Hanlin Hou / Kexin Wang / Zhenhua Shao / Cheng Deng / Feng Ye / Wei Yan / ![]() Abstract: Neuropeptide Y (NPY), a 36-amino-acid peptide, functions as a neurotransmitter in both the central and peripheral nervous systems by activating the NPY receptor subfamily. Notably, NPY analogs ...Neuropeptide Y (NPY), a 36-amino-acid peptide, functions as a neurotransmitter in both the central and peripheral nervous systems by activating the NPY receptor subfamily. Notably, NPY analogs display varying selectivity and exert diverse physiological effects through their interactions with this receptor family. [Pro]-NPY and [Leu, Pro]-NPY, mainly acting on YR, reportedly increases blood pressure and postsynaptically potentiates the effect of other vasoactive substances above all, while N-terminal cleaved NPY variants in human body primary mediates angiogenesis and neurotransmitter release inhibition through YR. However, the recognition mechanisms of YR and YR with specific agonists remain elusive, thereby hindering subtype receptor-selective drug development. In this study, we report three cryo-electron microscopy (cryo-EM) structures of Gi2-coupled YR and YR in complexes with NPY, as well as YR bound to a selective agonist [Leu, Pro]-NPY. Combined with cell-based assays, our study not only reveals the conserved peptide-binding mode of NPY receptors but also identifies an additional sub-pocket that confers ligand selectivity. Moreover, our analysis of YR evolutionary dynamics suggests that this sub-pocket has undergone functional adaptive evolution across different species. Collectively, our findings shed light on the molecular underpinnings of neuropeptide recognition and receptor activation, and they present a promising avenue for the design of selective drugs targeting the NPY receptor family. | |||||||||||||||||||||||||||||||||||||||||||||
History |
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Structure visualization
Structure viewer | Molecule: ![]() ![]() |
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Downloads & links
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Download
PDBx/mmCIF format | ![]() | 223.3 KB | Display | ![]() |
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PDB format | ![]() | 172.8 KB | Display | ![]() |
PDBx/mmJSON format | ![]() | Tree view | ![]() | |
Others | ![]() |
-Validation report
Summary document | ![]() | 1.2 MB | Display | ![]() |
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Full document | ![]() | 1.2 MB | Display | |
Data in XML | ![]() | 42.1 KB | Display | |
Data in CIF | ![]() | 63 KB | Display | |
Arichive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 36923MC ![]() 8k6nC ![]() 8k6oC M: map data used to model this data C: citing same article ( |
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Similar structure data | Similarity search - Function & homology ![]() |
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Links
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Assembly
Deposited unit | ![]()
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1 |
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Components
-Guanine nucleotide-binding protein ... , 3 types, 3 molecules ABC
#1: Protein | Mass: 40516.891 Da / Num. of mol.: 1 / Mutation: S47N,G204A,E246A,A327S Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() |
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#2: Protein | Mass: 39141.793 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() |
#3: Protein | Mass: 7861.143 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() |
-Neuropeptide ... , 2 types, 2 molecules DE
#4: Protein | Mass: 40569.445 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() |
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#6: Protein/peptide | Mass: 4278.720 Da / Num. of mol.: 1 / Source method: obtained synthetically / Source: (synth.) ![]() |
-Antibody , 1 types, 1 molecules S
#5: Antibody | Mass: 28636.793 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() ![]() |
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-Details
Has protein modification | Y |
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-Experimental details
-Experiment
Experiment | Method: ELECTRON MICROSCOPY |
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EM experiment | Aggregation state: PARTICLE / 3D reconstruction method: single particle reconstruction |
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Sample preparation
Component | Name: Structural complex of neuropeptide Y receptor 1 / Type: COMPLEX / Entity ID: all / Source: RECOMBINANT |
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Source (natural) | Organism: ![]() |
Source (recombinant) | Organism: ![]() ![]() |
Buffer solution | pH: 7.5 |
Specimen | Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES |
Vitrification | Cryogen name: ETHANE |
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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: ![]() |
Electron lens | Mode: BRIGHT FIELD / Nominal defocus max: 1800 nm / Nominal defocus min: 1000 nm |
Image recording | Electron dose: 57 e/Å2 / Film or detector model: GATAN K2 SUMMIT (4k x 4k) |
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Processing
EM software | Name: PHENIX / Category: model refinement | ||||||||||||||||||||||||
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CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION | ||||||||||||||||||||||||
3D reconstruction | Resolution: 3.3 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 127586 / Symmetry type: POINT | ||||||||||||||||||||||||
Refine LS restraints |
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