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Yorodumi- EMDB-32315: Cryo-EM structure of the neuromedin S-bound neuromedin U receptor... -
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Open data
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Basic information
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| Title | Cryo-EM structure of the neuromedin S-bound neuromedin U receptor 1-Gq protein complex | |||||||||
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 Keywords | Cryo-EM / GPCR / Neuromedin S / neuromedin U receptor 1 / Gq / complex / SIGNALING PROTEIN | |||||||||
| Function / homology |  Function and homology informationneuropeptide signaling pathway / Peptide ligand-binding receptors / 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 ...neuropeptide signaling pathway / Peptide ligand-binding receptors / 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 / 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 / GTPase binding / Ca2+ pathway / fibroblast proliferation / High laminar flow shear stress activates signaling by PIEZO1 and PECAM1:CDH5:KDR in endothelial cells / G alpha (i) signalling events / G alpha (s) signalling events / phospholipase C-activating G protein-coupled receptor signaling pathway / G alpha (q) signalling events / Ras protein signal transduction / Extra-nuclear estrogen signaling / cell population proliferation / G protein-coupled receptor signaling pathway / lysosomal membrane / GTPase activity / synapse / protein-containing complex binding / signal transduction / extracellular exosome / extracellular region / membrane / plasma membrane / cytoplasm / cytosol Similarity search - Function  | |||||||||
| Biological species |  Homo sapiens (human) | |||||||||
| Method | single particle reconstruction / cryo EM / Resolution: 2.9 Å | |||||||||
 Authors | You C / Xu HE | |||||||||
| Funding support |   China, 1 items 
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 Citation |  Journal: Nat Commun / Year: 2022Title: Structural insights into the peptide selectivity and activation of human neuromedin U receptors. Authors: Chongzhao You / Yumu Zhang / Peiyu Xu / Sijie Huang / Wanchao Yin / H Eric Xu / Yi Jiang / ![]() Abstract: Neuromedin U receptors (NMURs), including NMUR1 and NMUR2, are a group of G-coupled G protein-coupled receptors (GPCRs). NMUR1 and NMUR2 play distinct, pleiotropic physiological functions in ...Neuromedin U receptors (NMURs), including NMUR1 and NMUR2, are a group of G-coupled G protein-coupled receptors (GPCRs). NMUR1 and NMUR2 play distinct, pleiotropic physiological functions in peripheral tissues and in the central nervous system (CNS), respectively, according to their distinct tissue distributions. These receptors are stimulated by two endogenous neuropeptides, neuromedin U and S (NMU and NMS) with similar binding affinities. NMURs have gathered attention as potential drug targets for obesity and inflammatory disorders. Specifically, selective agonists for NMUR2 in peripheral tissue show promising long-term anti-obesity effects with fewer CNS-related side effects. However, the mechanisms of peptide binding specificity and receptor activation remain elusive. Here, we report four cryo-electron microscopy structures of G chimera-coupled NMUR1 and NMUR2 in complexes with NMU and NMS. These structures reveal the conserved overall peptide-binding mode and the mechanism of peptide selectivity for specific NMURs, as well as the common activation mechanism of the NMUR subfamily. Together, these findings provide insights into the molecular basis of the peptide recognition and offer an opportunity for the design of the selective drugs targeting NMURs.  | |||||||||
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Structure visualization
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Downloads & links
-EMDB archive
| Map data |  emd_32315.map.gz | 26.3 MB |  EMDB map data format | |
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| Header (meta data) |  emd-32315-v30.xml emd-32315.xml | 19 KB 19 KB  | Display Display  |  EMDB header | 
| Images |  emd_32315.png | 10.7 KB | ||
| Filedesc metadata |  emd-32315.cif.gz | 7 KB | ||
| Archive directory |  http://ftp.pdbj.org/pub/emdb/structures/EMD-32315 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-32315 | HTTPS FTP  | 
-Validation report
| Summary document |  emd_32315_validation.pdf.gz | 378.3 KB | Display |  EMDB validaton report | 
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| Full document |  emd_32315_full_validation.pdf.gz | 377.9 KB | Display | |
| Data in XML |  emd_32315_validation.xml.gz | 5.6 KB | Display | |
| Data in CIF |  emd_32315_validation.cif.gz | 6.4 KB | Display | |
| Arichive directory |  https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-32315 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-32315 | HTTPS FTP  | 
-Related structure data
| Related structure data | ![]() 7w56MC ![]() 7w53C ![]() 7w55C ![]() 7w57C 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_32315.map.gz / Format: CCP4 / Size: 30.5 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: 1.08 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 : the neuromedin S-bound neuromedin U receptor 1-Gq protein complex
| Entire | Name: the neuromedin S-bound neuromedin U receptor 1-Gq protein complex | 
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| Components | 
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-Supramolecule #1: the neuromedin S-bound neuromedin U receptor 1-Gq protein complex
| Supramolecule | Name: the neuromedin S-bound neuromedin U receptor 1-Gq protein complex type: complex / ID: 1 / Parent: 0 / Macromolecule list: all  | 
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| Source (natural) | Organism:  Homo sapiens (human) | 
-Macromolecule #1: Guanine nucleotide-binding protein G(q) subunit alpha
| Macromolecule | Name: Guanine nucleotide-binding protein G(q) subunit alpha / 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: 41.724383 KDa | 
| Recombinant expression | Organism:  Trichoplusia ni (cabbage looper) | 
| Sequence | String: MGCTLSAEDK AAVERSKMIE KQLQKDKQVY RRTLRLLLLG ADNSGKSTIV KQMRIYHVNG YSEEECKQYK AVVYSNTIQS  IIAIIRAMG RLKIDFGDSA RADDARQLFV LAGAAEEGFM TAELAGVIKR LWKDSGVQAC FNRSREYQLN DSAAYYLNDL D RIAQPNYI  ...String:  MGCTLSAEDK AAVERSKMIE KQLQKDKQVY RRTLRLLLLG ADNSGKSTIV KQMRIYHVNG YSEEECKQYK AVVYSNTIQS  IIAIIRAMG RLKIDFGDSA RADDARQLFV LAGAAEEGFM TAELAGVIKR LWKDSGVQAC FNRSREYQLN DSAAYYLNDL D RIAQPNYI PTQQDVLRTR VKTSGIFETK FQVDKVNFHM FDVGAQRDER RKWIQCFNDV TAIIFVVDSS DYNRLQEALN DF KSIWNNR WLRTISVILF LNKQDLLAEK VLAGKSKIED YFPEFARYTT PEDATPEPGE DPRVTRAKYF IRKEFVDIST ASG DGRHIC YPHFTCSVDT ENARRIFNDC KDIILQMNLR EYNLV  | 
-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: 40.226992 KDa | 
| Recombinant expression | Organism:  Trichoplusia ni (cabbage looper) | 
| Sequence | String: MGSLLQSELD QLRQEAEQLK NQIRDARKAC ADATLSQITN NIDPVGRIQM RTRRTLRGHL AKIYAMHWGT DSRLLVSASQ  DGKLIIWDS YTTNKVHAIP LRSSWVMTCA YAPSGNYVAC GGLDNICSIY NLKTREGNVR VSRELAGHTG YLSCCRFLDD N QIVTSSGD  ...String:  MGSLLQSELD QLRQEAEQLK NQIRDARKAC ADATLSQITN NIDPVGRIQM RTRRTLRGHL AKIYAMHWGT DSRLLVSASQ  DGKLIIWDS YTTNKVHAIP LRSSWVMTCA YAPSGNYVAC GGLDNICSIY NLKTREGNVR VSRELAGHTG YLSCCRFLDD N QIVTSSGD TTCALWDIET GQQTTTFTGH TGDVMSLSLA PDTRLFVSGA CDASAKLWDV REGMCRQTFT GHESDINAIC FF PNGNAFA TGSDDATCRL FDLRADQELM TYSHDNIICG ITSVSFSKSG RLLLAGYDDF NCNVWDALKA DRAGVLAGHD NRV SCLGVT DDGMAVATGS WDSFLKIWNG SSGGGGSGGG GSSGVSGWRL FKKIS UniProtKB: Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1  | 
-Macromolecule #3: Neuromedin-S
| Macromolecule | Name: Neuromedin-S / 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: 3.927453 KDa | 
| Recombinant expression | Organism:  Trichoplusia ni (cabbage looper) | 
| Sequence | String:  ILQRGSGTAA VDFTKKDHTA TWGRPFFLFR PRNQ UniProtKB: Neuromedin-S  | 
-Macromolecule #4: scFv16
| Macromolecule | Name: scFv16 / 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: 26.496514 KDa | 
| Recombinant expression | Organism:  Trichoplusia ni (cabbage looper) | 
| Sequence | String: DVQLVESGGG LVQPGGSRKL SCSASGFAFS SFGMHWVRQA PEKGLEWVAY ISSGSGTIYY ADTVKGRFTI SRDDPKNTLF  LQMTSLRSE DTAMYYCVRS IYYYGSSPFD FWGQGTTLTV SSGGGGSGGG GSGGGSSDIV MTQATSSVPV TPGESVSISC R SSKSLLHS  ...String:  DVQLVESGGG LVQPGGSRKL SCSASGFAFS SFGMHWVRQA PEKGLEWVAY ISSGSGTIYY ADTVKGRFTI SRDDPKNTLF  LQMTSLRSE DTAMYYCVRS IYYYGSSPFD FWGQGTTLTV SSGGGGSGGG GSGGGSSDIV MTQATSSVPV TPGESVSISC R SSKSLLHS NGNTYLYWFL QRPGQSPQLL IYRMSNLASG VPDRFSGSGS GTAFTLTISR LEAEDVGVYY CMQHLEYPLT FG AGTKLEL K  | 
-Macromolecule #5: 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: 5 / Number of copies: 1 / Enantiomer: LEVO  | 
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| Source (natural) | Organism:  Homo sapiens (human) | 
| Molecular weight | Theoretical: 7.729947 KDa | 
| Recombinant expression | Organism:  Trichoplusia ni (cabbage looper) | 
| Sequence | String:  ASNNTASIAQ ARKLVEQLKM EANIDRIKVS KAAADLMAYC EAHAKEDPLL TPVPASENPF REKKFFCAIL UniProtKB: Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2  | 
-Macromolecule #6: Neuromedin U Receptor 1
| Macromolecule | Name: Neuromedin U Receptor 1 / type: protein_or_peptide / ID: 6 / Number of copies: 1 / Enantiomer: LEVO | 
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| Source (natural) | Organism:  Homo sapiens (human) | 
| Molecular weight | Theoretical: 83.678484 KDa | 
| Recombinant expression | Organism:  Trichoplusia ni (cabbage looper) | 
| Sequence | String: MKTIIALSYI FCLVFADYKD DDDAKLQTMH HHHHHHHHHA DLEDNWETLN DNLKVIEKAD NAAQVKDALT KMRAAALDAQ  KATPPKLED KSPDSPEMKD FRHGFDILVG QIDDALKLAN EGKVKEAQAA AEQLKTTRNA YIQKYLASEN LYFQGGTMTP L CLNCSVLP  ...String:  MKTIIALSYI FCLVFADYKD DDDAKLQTMH HHHHHHHHHA DLEDNWETLN DNLKVIEKAD NAAQVKDALT KMRAAALDAQ  KATPPKLED KSPDSPEMKD FRHGFDILVG QIDDALKLAN EGKVKEAQAA AEQLKTTRNA YIQKYLASEN LYFQGGTMTP L CLNCSVLP GDLYPGGARN PMACNGSAAR GHFDPEDLNL TDEALRLKYL GPQQTELFMP ICATYLLIFV VGAVGNGLTC LV ILRHKAM RTPTNYYLFS LAVSDLLVLL VGLPLELYEM WHNYPFLLGV GGCYFRTLLF EMVCLASVLN VTALSVERYV AVV HPLQAR SMVTRAHVRR VLGAVWGLAM LCSLPNTSLH GIRQLHVPCR GPVPDSAVCM LVRPRALYNM VVQTTALLFF CLPM AIMSV LYLLIGLRLR RERLLLMQEA KGRGSAAARS RYTCRLQQHD RGRRQVTKML FVLVVVFGIC WAPFHADRVM WSVVS QWTD GLHLAFQHVH VISGIFFYLG SAANPVLYSL MSSRFRETFQ EALCLGACCH RLRPRHSSHS LSRMTTGSTL CDVGSL GSW VHPLAGNDGP EAQQETDPSG SSGGGGSGGG GSSGVFTLED FVGDWEQTAA YNLDQVLEQG GVSSLLQNLA VSVTPIQ RI VRSGENALKI DIHVIIPYEG LSADQMAQIE EVFKVVYPVD DHHFKVILPY GTLVIDGVTP NMLNYFGRPY EGIAVFDG K KITVTGTLWN GNKIIDERLI TPDGSMLFRV TINS  | 
-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: 7.4 | 
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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 (6k x 4k) / Average electron dose: 61.8 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: 2.2 µm / Nominal defocus min: 1.1 µm | 
| Experimental equipment | ![]() Model: Titan Krios / Image courtesy: FEI Company  | 
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Keywords
Homo sapiens (human)
Authors
China, 1 items 
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Y (Row.)
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Trichoplusia ni (cabbage looper)
Processing
FIELD EMISSION GUN
