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Yorodumi- EMDB-33071: Cryo-EM structure of neuropeptide Y Y4 receptor in complex with P... -
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Basic information
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| Title | Cryo-EM structure of neuropeptide Y Y4 receptor in complex with PP and Gi | ||||||||||||
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| Function / homology | Function and homology informationpancreatic polypeptide receptor activity / neuropeptide Y receptor binding / neuropeptide hormone activity / neuropeptide binding / feeding behavior / peptide hormone binding / protein secretion / neuropeptide signaling pathway / adenylate cyclase inhibitor activity / positive regulation of protein localization to cell cortex ...pancreatic polypeptide receptor activity / neuropeptide Y receptor binding / neuropeptide hormone activity / neuropeptide binding / feeding behavior / peptide hormone binding / protein secretion / neuropeptide signaling pathway / adenylate cyclase inhibitor activity / positive regulation of protein localization to cell cortex / Adenylate cyclase inhibitory pathway / T cell migration / D2 dopamine receptor binding / response to prostaglandin E / adenylate cyclase regulator activity / G protein-coupled serotonin receptor binding / adenylate cyclase-inhibiting serotonin receptor signaling pathway / cellular response to forskolin / regulation of mitotic spindle organization / Peptide ligand-binding receptors / Regulation of insulin secretion / positive regulation of cholesterol biosynthetic process / negative regulation of insulin secretion / G protein-coupled receptor binding / G protein-coupled receptor activity / response to peptide hormone / adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway / hormone activity / adenylate cyclase-modulating G protein-coupled receptor signaling pathway / G-protein beta/gamma-subunit complex binding / centriolar satellite / 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 / Activation of G protein gated Potassium channels / Inhibition of voltage gated Ca2+ channels via Gbeta/gamma subunits / G-protein activation / 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 / photoreceptor disc membrane / Sensory perception of sweet, bitter, and umami (glutamate) taste / Glucagon-type ligand receptors / Adrenaline,noradrenaline inhibits insulin secretion / Vasopressin regulates renal water homeostasis via Aquaporins / GDP binding / 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 / Cooperation of PDCL (PhLP1) and TRiC/CCT in G-protein beta folding / 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 / G protein activity / GTPase binding / Ca2+ pathway / fibroblast proliferation / midbody / 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 / phospholipase C-activating G protein-coupled receptor signaling pathway / G alpha (q) signalling events / Hydrolases; Acting on acid anhydrides; Acting on GTP to facilitate cellular and subcellular movement / Ras protein signal transduction / Extra-nuclear estrogen signaling / cell population proliferation / neuron projection / ciliary basal body / G protein-coupled receptor signaling pathway / lysosomal membrane / cell division / GTPase activity / synapse / centrosome / GTP binding / protein-containing complex binding / nucleolus / magnesium ion binding / Golgi apparatus / signal transduction 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: 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. | ||||||||||||
| History |
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Structure visualization
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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 ( |
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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_33071.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: 1.045 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 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 |
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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 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 |
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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 |
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About Yorodumi



Homo sapiens (human)
Authors
China, 3 items
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Z (Sec.)
Y (Row.)
X (Col.)




















Trichoplusia ni (cabbage looper)
FIELD EMISSION GUN
