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Yorodumi- EMDB-33071: Cryo-EM structure of neuropeptide Y Y4 receptor in complex with P... -
+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-33071 | ||||||||||||
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Title | Cryo-EM structure of neuropeptide Y Y4 receptor in complex with PP and Gi | ||||||||||||
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Sample |
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Function / homology | Function and homology information pancreatic polypeptide receptor activity / neuropeptide Y receptor binding / neuropeptide hormone activity / feeding behavior / plasma membrane => GO:0005886 / peptide hormone binding / neuropeptide signaling pathway / protein secretion / Adenylate cyclase inhibitory pathway / positive regulation of protein localization to cell cortex ...pancreatic polypeptide receptor activity / neuropeptide Y receptor binding / neuropeptide hormone activity / feeding behavior / plasma membrane => GO:0005886 / peptide hormone binding / neuropeptide signaling pathway / protein secretion / Adenylate cyclase inhibitory pathway / positive regulation of protein localization to cell cortex / regulation of cAMP-mediated signaling / D2 dopamine receptor binding / G protein-coupled serotonin receptor binding / regulation of mitotic spindle organization / cellular response to forskolin / adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway / Peptide ligand-binding receptors / 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-coupled acetylcholine receptor signaling pathway / G-protein activation / hormone activity / 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 / response to peptide hormone / ADP signalling through P2Y purinoceptor 12 / G beta:gamma signalling through BTK / Synthesis, secretion, and inactivation of Glucagon-like Peptide-1 (GLP-1) / 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 / GPER1 signaling / GDP binding / G-protein beta-subunit binding / Inactivation, recovery and regulation of the phototransduction cascade / heterotrimeric G-protein complex / 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 / Ca2+ pathway / phospholipase C-activating G protein-coupled receptor signaling pathway / cell cortex / midbody / G alpha (i) signalling events / fibroblast proliferation / G alpha (s) signalling events / G alpha (q) signalling events / Ras protein signal transduction / Extra-nuclear estrogen signaling / cell population proliferation / G protein-coupled receptor signaling pathway / cell division / lysosomal membrane / GTPase activity / centrosome / synapse / protein-containing complex binding / nucleolus / GTP binding / magnesium ion binding / signal transduction / extracellular space / extracellular exosome / extracellular region / nucleoplasm / membrane / plasma membrane / cytoplasm / cytosol Similarity search - Function | ||||||||||||
Biological species | Homo sapiens (human) | ||||||||||||
Method | single particle reconstruction / cryo EM / Resolution: 3.0 Å | ||||||||||||
Authors | Tang T / Han S / Zhao Q / Wu B | ||||||||||||
Funding support | China, 3 items
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Citation | Journal: Sci Adv / Year: 2022 Title: 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. | ||||||||||||
History |
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-Structure visualization
Supplemental images |
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-Downloads & links
-EMDB archive
Map data | emd_33071.map.gz | 59.8 MB | EMDB map data format | |
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Header (meta data) | emd-33071-v30.xml emd-33071.xml | 16.4 KB 16.4 KB | Display Display | EMDB header |
Images | emd_33071.png | 69 KB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-33071 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-33071 | HTTPS FTP |
-Validation report
Summary document | emd_33071_validation.pdf.gz | 442.4 KB | Display | EMDB validaton report |
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Full document | emd_33071_full_validation.pdf.gz | 441.9 KB | Display | |
Data in XML | emd_33071_validation.xml.gz | 6 KB | Display | |
Data in CIF | emd_33071_validation.cif.gz | 6.8 KB | Display | |
Arichive directory | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-33071 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-33071 | HTTPS FTP |
-Related structure data
Related structure data | 7x9cMC 7x9aC 7x9bC M: atomic model generated by this map C: citing same article (ref.) |
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Similar structure data | Similarity search - Function & homologyF&H Search |
-Links
EMDB pages | EMDB (EBI/PDBe) / EMDataResource |
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Related items in Molecule of the Month |
-Map
File | Download / File: emd_33071.map.gz / Format: CCP4 / Size: 64 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||
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Voxel size | X=Y=Z: 1.045 Å | ||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||
Details | EMDB XML:
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-Supplemental data
-Sample components
-Entire : Neuropeptide Y Y4 receptor in complex with PP and Gi
Entire | Name: Neuropeptide Y Y4 receptor in complex with PP and Gi |
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Components |
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-Supramolecule #1: Neuropeptide Y Y4 receptor in complex with PP and Gi
Supramolecule | Name: Neuropeptide Y Y4 receptor in complex with PP 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 Y4 receptor and Gi
Supramolecule | Name: Neuropeptide Y Y4 receptor and Gi / type: complex / Chimera: Yes / ID: 2 / Parent: 1 / Macromolecule list: #1-#4 |
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-Supramolecule #3: pancreatic polypeptide
Supramolecule | Name: pancreatic polypeptide / type: complex / Chimera: Yes / ID: 3 / Parent: 1 / Macromolecule list: #5 |
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-Macromolecule #1: Neuropeptide Y receptor type 4
Macromolecule | Name: Neuropeptide Y receptor type 4 / 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: 42.755215 KDa |
Recombinant expression | Organism: Trichoplusia ni (cabbage looper) |
Sequence | String: MNTSHLLALL LPKSPQGENR SKPLGTPYNF SEHCQDSVDV MVFIVTSYSI ETVVGVLGNL CLMCVTVRQK EKANVTNLLI ANLAFSDFL MCLLCQPLTA VYTIMDYWIF GETLCKMSAF IQCMSVTVSI LSLVLVALER HQLIINPTGW KPSISQAYLG I VLIWVIAC ...String: MNTSHLLALL LPKSPQGENR SKPLGTPYNF SEHCQDSVDV MVFIVTSYSI ETVVGVLGNL CLMCVTVRQK EKANVTNLLI ANLAFSDFL MCLLCQPLTA VYTIMDYWIF GETLCKMSAF IQCMSVTVSI LSLVLVALER HQLIINPTGW KPSISQAYLG I VLIWVIAC VLSLPFLANS ILENVFHKNH SKALEFLADK VVCTESWPLA HHRTIYTTFL LLFQYCLPLG FILVCYARIY RR LQRQGRV FHKGTYSLRA GHMKQVNVVL VVMVVAFAVL WLPLHVFNSL EDWHHEAIPI CHGNLIFLVC HLLAMASTCV NPF IYGFLN TNFKKEIKAL VLTCQQEFLE VLFQGPWSHP QFEKGGGSGG GSGGSAWSHP QFEK |
-Macromolecule #2: 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: 2 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: Homo sapiens (human) |
Molecular weight | Theoretical: 40.447141 KDa |
Recombinant expression | Organism: Trichoplusia ni (cabbage looper) |
Sequence | String: MGCTLSAEDK AAVERSKMID RNLREDGEKA AREVKLLLLG AGESGKCTIV KQMKIIHEAG YSEEECKQYK AVVYSNTIQS IIAIIRAMG RLKIDFGDSA RADDARQLFV LAGAAEEGFM TAELAGVIKR LWKDSGVQAC FNRSREYQLN DSAAYYLNDL D RIAQPNYI ...String: MGCTLSAEDK AAVERSKMID RNLREDGEKA AREVKLLLLG AGESGKCTIV KQMKIIHEAG YSEEECKQYK AVVYSNTIQS IIAIIRAMG RLKIDFGDSA RADDARQLFV LAGAAEEGFM TAELAGVIKR LWKDSGVQAC FNRSREYQLN DSAAYYLNDL D RIAQPNYI PTQQDVLRTR VKTTGIVETH FTFKDLHFKM FDVTAQRSER KKWIHCFEGV TAIIFCVALS DYDLVLAEDE EM NRMHASM KLFDSICNNK WFTDTSIILF LNKKDLFEEK IKKSPLTICY PEYAGSNTYE EAAAYIQCQF EDLNKRKDTK EIY THFTCS TDTKNVQFVF DAVTDVIIKN NLKDCGLF |
-Macromolecule #3: 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: 3 / 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 #4: 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: 4 / 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 #5: Pancreatic hormone
Macromolecule | Name: Pancreatic hormone / 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: 4.185743 KDa |
Sequence | String: APLEPVYPGD NATPEQMAQY AADLRRYINM LTRPR(TYC) |
-Experimental details
-Structure determination
Method | cryo EM |
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Processing | single particle reconstruction |
Aggregation state | particle |
-Sample preparation
Buffer | pH: 7.5 |
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Vitrification | Cryogen name: ETHANE |
-Electron microscopy
Microscope | FEI TITAN KRIOS |
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Image recording | Film or detector model: GATAN K3 BIOQUANTUM (6k x 4k) / Average electron dose: 70.0 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: 1.5 µm / Nominal defocus min: 0.8 µm |
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |
-Image processing
Final reconstruction | Resolution.type: BY AUTHOR / Resolution: 3.0 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 1047385 |
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Initial angle assignment | Type: MAXIMUM LIKELIHOOD |
Final angle assignment | Type: MAXIMUM LIKELIHOOD |