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Yorodumi- EMDB-33070: Cryo-EM structure of neuropeptide Y Y2 receptor in complex with N... -
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Basic information
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| Title | Cryo-EM structure of neuropeptide Y Y2 receptor in complex with NPY and Gi | ||||||||||||
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| Function / homology | Function and homology informationnegative regulation of nervous system process / regulation of nerve growth factor production / peptide YY receptor activity / short-day photoperiodism / negative regulation of acute inflammatory response to antigenic stimulus / positive regulation of circadian sleep/wake cycle, non-REM sleep / positive regulation of peptide secretion / neuropeptide Y receptor activity / monocyte activation / positive regulation of dopamine metabolic process ...negative regulation of nervous system process / regulation of nerve growth factor production / peptide YY receptor activity / short-day photoperiodism / negative regulation of acute inflammatory response to antigenic stimulus / positive regulation of circadian sleep/wake cycle, non-REM sleep / positive regulation of peptide secretion / neuropeptide Y receptor activity / monocyte activation / positive regulation of dopamine metabolic process / : / neuropeptide Y receptor binding / intestinal epithelial cell differentiation / negative regulation of secretion / positive regulation of eating behavior / positive regulation of appetite / cardiac left ventricle morphogenesis / synaptic signaling via neuropeptide / adult feeding behavior / regulation of presynaptic cytosolic calcium ion concentration / positive regulation of smooth muscle contraction / drinking behavior / negative regulation of excitatory postsynaptic potential / positive regulation of dopamine secretion / neuropeptide hormone activity / positive regulation of cell-substrate adhesion / feeding behavior / non-motile cilium / negative regulation of synaptic transmission, glutamatergic / negative regulation of feeding behavior / regulation of synaptic vesicle exocytosis / central nervous system neuron development / outflow tract morphogenesis / locomotory exploration behavior / developmental growth / nitric oxide mediated signal transduction / FOXO-mediated transcription of oxidative stress, metabolic and neuronal genes / G protein-coupled receptor signaling pathway, coupled to cyclic nucleotide second messenger / neuronal dense core vesicle / behavioral fear response / negative regulation of cAMP/PKA signal transduction / adenylate cyclase inhibitor activity / positive regulation of protein localization to cell cortex / negative regulation of blood pressure / T cell migration / positive regulation of relaxation of smooth muscle / Adenylate cyclase inhibitory pathway / D2 dopamine receptor binding / adenylate cyclase-inhibiting serotonin receptor signaling pathway / G protein-coupled serotonin receptor binding / cellular response to forskolin / Peptide ligand-binding receptors / regulation of mitotic spindle organization / chemokine-mediated signaling pathway / calcium channel regulator activity / Regulation of insulin secretion / neuropeptide signaling pathway / response to prostaglandin E / locomotory behavior / positive regulation of cholesterol biosynthetic process / cerebral cortex development / negative regulation of insulin secretion / G protein-coupled receptor binding / response to peptide hormone / G protein-coupled receptor activity / GABA-ergic synapse / adenylate cyclase-modulating G protein-coupled receptor signaling pathway / G-protein beta/gamma-subunit complex binding / centriolar satellite / adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway / Olfactory Signaling Pathway / Activation of the phototransduction cascade / G protein-coupled acetylcholine receptor signaling pathway / neuron projection development / G beta:gamma signalling through PLC beta / Presynaptic function of Kainate receptors / Thromboxane signalling through TP receptor / terminal bouton / Activation of G protein gated Potassium channels / Inhibition of voltage gated Ca2+ channels via Gbeta/gamma subunits / G-protein activation / Glucagon signaling in metabolic regulation / G beta:gamma signalling through CDC42 / Prostacyclin signalling through prostacyclin receptor / G beta:gamma signalling through BTK / Synthesis, secretion, and inactivation of Glucagon-like Peptide-1 (GLP-1) / photoreceptor disc membrane / ADP signalling through P2Y purinoceptor 12 / Sensory perception of sweet, bitter, and umami (glutamate) taste / Glucagon-type ligand receptors / GDP binding / Adrenaline,noradrenaline inhibits insulin secretion / Vasopressin regulates renal water homeostasis via Aquaporins / Glucagon-like Peptide-1 (GLP1) regulates insulin secretion / G alpha (z) signalling events / cellular response to catecholamine stimulus / ADP signalling through P2Y purinoceptor 1 / ADORA2B mediated anti-inflammatory cytokines production / G beta:gamma signalling through PI3Kgamma / adenylate cyclase-activating dopamine receptor signaling pathway Similarity search - Function | ||||||||||||
| Biological species | Homo sapiens (human) | ||||||||||||
| Method | single particle reconstruction / cryo EM / Resolution: 3.4 Å | ||||||||||||
Authors | Tang T / Han S / Zhao Q / Wu B | ||||||||||||
| Funding support | China, 3 items
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Citation | Journal: Sci Adv / Year: 2022Title: 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. | ||||||||||||
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Structure visualization
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Downloads & links
-EMDB archive
| Map data | emd_33070.map.gz | 59.5 MB | EMDB map data format | |
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| Header (meta data) | emd-33070-v30.xml emd-33070.xml | 16.5 KB 16.5 KB | Display Display | EMDB header |
| Images | emd_33070.png | 42.6 KB | ||
| Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-33070 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-33070 | HTTPS FTP |
-Related structure data
| Related structure data | ![]() 7x9bMC ![]() 7x9aC ![]() 7x9cC M: atomic model generated by this map C: citing same article ( |
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| Similar structure data | Similarity search - Function & homology F&H Search |
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Links
| EMDB pages | EMDB (EBI/PDBe) / EMDataResource |
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| Related items in Molecule of the Month |
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Map
| File | Download / File: emd_33070.map.gz / Format: CCP4 / Size: 64 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||
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| Projections & slices | Image control
Images are generated by Spider. | ||||||||||||||||||||||||||||||||||||
| Voxel size | X=Y=Z: 0.82 Å | ||||||||||||||||||||||||||||||||||||
| Density |
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| Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||
| Details | EMDB XML:
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-Supplemental data
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Sample components
-Entire : Neuropeptide Y Y2 receptor in complex with NPY and Gi
| Entire | Name: Neuropeptide Y Y2 receptor in complex with NPY and Gi |
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| Components |
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-Supramolecule #1: Neuropeptide Y Y2 receptor in complex with NPY and Gi
| Supramolecule | Name: Neuropeptide Y Y2 receptor in complex with NPY and Gi / type: complex / Chimera: Yes / ID: 1 / Parent: 0 / Macromolecule list: all |
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| Source (natural) | Organism: Homo sapiens (human) |
-Supramolecule #2: Neuropeptide Y Y2 receptor and Gi
| Supramolecule | Name: Neuropeptide Y Y2 receptor and Gi / type: complex / Chimera: Yes / ID: 2 / Parent: 1 / Macromolecule list: #1-#4 |
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-Supramolecule #3: Neuropeptide Y
| Supramolecule | Name: Neuropeptide Y / type: complex / Chimera: Yes / ID: 3 / Parent: 1 / Macromolecule list: #5 |
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-Macromolecule #1: Guanine nucleotide-binding protein G(i) subunit alpha-1
| Macromolecule | Name: Guanine nucleotide-binding protein G(i) subunit alpha-1 type: protein_or_peptide / ID: 1 / Number of copies: 1 / Enantiomer: LEVO |
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| Source (natural) | Organism: Homo sapiens (human) |
| Molecular weight | Theoretical: 40.414047 KDa |
| Recombinant expression | Organism: Trichoplusia ni (cabbage looper) |
| Sequence | String: MGCTLSAEDK AAVERSKMID RNLREDGEKA AREVKLLLLG AGESGKNTIV KQMKIIHEAG YSEEECKQYK AVVYSNTIQS IIAIIRAMG RLKIDFGDSA RADDARQLFV LAGAAEEGFM TAELAGVIKR LWKDSGVQAC FNRSREYQLN DSAAYYLNDL D RIAQPNYI ...String: MGCTLSAEDK AAVERSKMID RNLREDGEKA AREVKLLLLG AGESGKNTIV KQMKIIHEAG YSEEECKQYK AVVYSNTIQS IIAIIRAMG RLKIDFGDSA RADDARQLFV LAGAAEEGFM TAELAGVIKR LWKDSGVQAC FNRSREYQLN DSAAYYLNDL D RIAQPNYI PTQQDVLRTR VKTTGIVETH FTFKDLHFKM FDVGAQRSER KKWIHCFEGV TAIIFCVALS DYDLVLAEDE EM NRMHASM KLFDSICNNK WFTDTSIILF LNKKDLFEEK IKKSPLTICY PEYAGSNTYE EAAAYIQCQF EDLNKRKDTK EIY THFTCS TDTKNVQFVF DAVTDVIIKN NLKDCGLF |
-Macromolecule #2: Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1
| Macromolecule | Name: Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1 type: protein_or_peptide / ID: 2 / Number of copies: 1 / Enantiomer: LEVO |
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| Source (natural) | Organism: Homo sapiens (human) |
| Molecular weight | Theoretical: 38.744371 KDa |
| Recombinant expression | Organism: Trichoplusia ni (cabbage looper) |
| Sequence | String: MHHHHHHGSL LQSELDQLRQ EAEQLKNQIR DARKACADAT LSQITNNIDP VGRIQMRTRR TLRGHLAKIY AMHWGTDSRL LVSASQDGK LIIWDSYTTN KVHAIPLRSS WVMTCAYAPS GNYVACGGLD NICSIYNLKT REGNVRVSRE LAGHTGYLSC C RFLDDNQI ...String: MHHHHHHGSL LQSELDQLRQ EAEQLKNQIR DARKACADAT LSQITNNIDP VGRIQMRTRR TLRGHLAKIY AMHWGTDSRL LVSASQDGK LIIWDSYTTN KVHAIPLRSS WVMTCAYAPS GNYVACGGLD NICSIYNLKT REGNVRVSRE LAGHTGYLSC C RFLDDNQI VTSSGDTTCA LWDIETGQQT TTFTGHTGDV MSLSLAPDTR LFVSGACDAS AKLWDVREGM CRQTFTGHES DI NAICFFP NGNAFATGSD DATCRLFDLR ADQELMTYSH DNIICGITSV SFSKSGRLLL AGYDDFNCNV WDALKADRAG VLA GHDNRV SCLGVTDDGM AVATGSWDSF LKIWN |
-Macromolecule #3: Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2
| Macromolecule | Name: Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2 type: protein_or_peptide / ID: 3 / Number of copies: 1 / Enantiomer: LEVO |
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| Source (natural) | Organism: Homo sapiens (human) |
| Molecular weight | Theoretical: 7.861143 KDa |
| Recombinant expression | Organism: Trichoplusia ni (cabbage looper) |
| Sequence | String: MASNNTASIA QARKLVEQLK MEANIDRIKV SKAAADLMAY CEAHAKEDPL LTPVPASENP FREKKFFCAI L |
-Macromolecule #4: Neuropeptide Y receptor type 2
| Macromolecule | Name: Neuropeptide Y receptor type 2 / type: protein_or_peptide / ID: 4 / Number of copies: 1 / Enantiomer: LEVO |
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| Source (natural) | Organism: Homo sapiens (human) |
| Molecular weight | Theoretical: 43.737883 KDa |
| Recombinant expression | Organism: Trichoplusia ni (cabbage looper) |
| Sequence | String: MGPIGAEADE NQTVEEMKVE QYGPQTTPRG ELVPDPEPEL IDSTKLIEVQ VVLILAYCSI ILLGVIGNSL VIHVVIKFKS MRTVTNFFI ANLAVADLLV NTLCLPFTLT YTLMGEWKMG PVLCHLVPYA QGLAVQVSTI TLTVIALDRH RCIVYHLESK I SKRISFLI ...String: MGPIGAEADE NQTVEEMKVE QYGPQTTPRG ELVPDPEPEL IDSTKLIEVQ VVLILAYCSI ILLGVIGNSL VIHVVIKFKS MRTVTNFFI ANLAVADLLV NTLCLPFTLT YTLMGEWKMG PVLCHLVPYA QGLAVQVSTI TLTVIALDRH RCIVYHLESK I SKRISFLI IGLAWGISAL LASPLAIFRE YSLIEIIPDF EIVACTEKWP GEEKSIYGTV YSLSSLLILY VLPLGIISFS YT RIWSKLK NHVSPGAAND HYHQRRQKTT KMLVCVVVVF AVSWLPLHAF QLAVDIDSQV LDLKEYKLIF TVFHIIAMCS TFA NPLLYG WMNSNYRKAF LSAFRCEQRL DAIHSEVEFL EVLFQGPWSH PQFEKGGGSG GGSGGSAWSH PQFEK |
-Macromolecule #5: Neuropeptide Y
| Macromolecule | Name: Neuropeptide Y / type: protein_or_peptide / ID: 5 / Number of copies: 1 / Enantiomer: LEVO |
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| Source (natural) | Organism: Homo sapiens (human) |
| Molecular weight | Theoretical: 4.277735 KDa |
| Sequence | String: YPSKPDNPGE DAPAEDMARY YSALRHYINL ITRQR(TYC) |
-Experimental details
-Structure determination
| Method | cryo EM |
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Processing | single particle reconstruction |
| Aggregation state | particle |
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Sample preparation
| Buffer | pH: 7.5 |
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| Vitrification | Cryogen name: ETHANE |
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Electron microscopy
| Microscope | FEI TITAN KRIOS |
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| Image recording | Film or detector model: GATAN K2 SUMMIT (4k x 4k) / Average electron dose: 60.0 e/Å2 |
| Electron beam | Acceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN |
| Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Nominal defocus max: 2.3000000000000003 µm / Nominal defocus min: 1.3 µm |
| Experimental equipment | ![]() Model: Titan Krios / Image courtesy: FEI Company |
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Image processing
| Final reconstruction | Resolution.type: BY AUTHOR / Resolution: 3.4 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 361477 |
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| Initial angle assignment | Type: MAXIMUM LIKELIHOOD |
| Final angle assignment | Type: MAXIMUM LIKELIHOOD |
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About Yorodumi



Homo sapiens (human)
Authors
China, 3 items
Citation







































Z (Sec.)
Y (Row.)
X (Col.)




















Trichoplusia ni (cabbage looper)
FIELD EMISSION GUN
