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Yorodumi- EMDB-32314: Cryo-EM structure of the neuromedin U-bound neuromedin U receptor... -
+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-32314 | |||||||||
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Title | Cryo-EM structure of the neuromedin U-bound neuromedin U receptor 2-Gq protein complex | |||||||||
Map data | ||||||||||
Sample |
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Function / homology | Function and homology information type 1 neuromedin U receptor binding / type 2 neuromedin U receptor binding / neuromedin U receptor binding / regulation of feeding behavior / regulation of grooming behavior / positive regulation of smooth muscle contraction / temperature homeostasis / neuropeptide signaling pathway / positive regulation of synaptic transmission / energy homeostasis ...type 1 neuromedin U receptor binding / type 2 neuromedin U receptor binding / neuromedin U receptor binding / regulation of feeding behavior / regulation of grooming behavior / positive regulation of smooth muscle contraction / temperature homeostasis / neuropeptide signaling pathway / positive regulation of synaptic transmission / energy homeostasis / 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 activation / G protein-coupled acetylcholine receptor signaling pathway / Activation of G protein gated Potassium channels / Inhibition of voltage gated Ca2+ channels via Gbeta/gamma subunits / terminal bouton / Prostacyclin signalling through prostacyclin receptor / Glucagon signaling in metabolic regulation / G beta:gamma signalling through CDC42 / 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 / 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 / phospholipase C-activating G protein-coupled receptor signaling pathway / Ca2+ pathway / G alpha (i) signalling events / fibroblast proliferation / G alpha (s) signalling events / G alpha (q) signalling events / cell population proliferation / Ras protein signal transduction / Extra-nuclear estrogen signaling / G protein-coupled receptor signaling pathway / lysosomal membrane / signaling receptor binding / 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: 2.8 Å | |||||||||
Authors | You C / Xu HE / Jiang Y | |||||||||
Funding support | China, 1 items
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Citation | Journal: Nat Commun / Year: 2022 Title: 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. | |||||||||
History |
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-Structure visualization
Supplemental images |
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-Downloads & links
-EMDB archive
Map data | emd_32314.map.gz | 26.2 MB | EMDB map data format | |
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Header (meta data) | emd-32314-v30.xml emd-32314.xml | 15.6 KB 15.6 KB | Display Display | EMDB header |
Images | emd_32314.png | 24.1 KB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-32314 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-32314 | HTTPS FTP |
-Validation report
Summary document | emd_32314_validation.pdf.gz | 332.9 KB | Display | EMDB validaton report |
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Full document | emd_32314_full_validation.pdf.gz | 332.5 KB | Display | |
Data in XML | emd_32314_validation.xml.gz | 5.6 KB | Display | |
Data in CIF | emd_32314_validation.cif.gz | 6.4 KB | Display | |
Arichive directory | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-32314 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-32314 | HTTPS FTP |
-Related structure data
Related structure data | 7w55MC 7w53C 7w56C 7w57C 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_32314.map.gz / Format: CCP4 / Size: 30.5 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||
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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
-Sample components
-Entire : the neuromedin U-bound neuromedin U receptor 2-Gq protein complex
Entire | Name: the neuromedin U-bound neuromedin U receptor 2-Gq protein complex |
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Components |
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-Supramolecule #1: the neuromedin U-bound neuromedin U receptor 2-Gq protein complex
Supramolecule | Name: the neuromedin U-bound neuromedin U receptor 2-Gq protein complex type: complex / ID: 1 / Parent: 0 / Macromolecule list: all |
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Source (natural) | Organism: Homo sapiens (human) |
Recombinant expression | Organism: Trichoplusia ni (cabbage looper) |
-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: 37.915496 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 WDSFLKIWN |
-Macromolecule #3: Neuromedin-U-25
Macromolecule | Name: Neuromedin-U-25 / 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: 3.213519 KDa |
Recombinant expression | Organism: Trichoplusia ni (cabbage looper) |
Sequence | String: FRVDEEFQSP FASQSRGYFL FRPRNQ |
-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: 26.466486 KDa |
Recombinant expression | Organism: Trichoplusia ni (cabbage looper) |
Sequence | String: DVQLVESGGG LVQPGGSRKL SCSASGFAFS SFGMHWVRQA PEKGLEWVAY ISSGSGTIYY ADTVKGRFTI SRDDPKNTLF LQMTSLRSE DTAMYYCVRS IYYYGSSPFD FWGQGTTLTV SSGGGGSGGG GSGGGGSDIV MTQATSSVPV TPGESVSISC R SSKSLLHS ...String: DVQLVESGGG LVQPGGSRKL SCSASGFAFS SFGMHWVRQA PEKGLEWVAY ISSGSGTIYY ADTVKGRFTI SRDDPKNTLF LQMTSLRSE DTAMYYCVRS IYYYGSSPFD FWGQGTTLTV SSGGGGSGGG GSGGGGSDIV 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 |
-Macromolecule #6: Neuromedin-U receptor 2
Macromolecule | Name: Neuromedin-U receptor 2 / 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: 65.417359 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 LYFQGGTMSG M EKLQNASW ...String: MKTIIALSYI FCLVFADYKD DDDAKLQTMH HHHHHHHHHA DLEDNWETLN DNLKVIEKAD NAAQVKDALT KMRAAALDAQ KATPPKLED KSPDSPEMKD FRHGFDILVG QIDDALKLAN EGKVKEAQAA AEQLKTTRNA YIQKYLASEN LYFQGGTMSG M EKLQNASW IYQQKLEDPF QKHLNSTEEY LAFLCGPRRS HFFLPVSVVY VPIFVVGVIG NVLVCLVILQ HQAMKTPTNY YL FSLAVSD LLVLLLGMPL EVYEMWRNYP FLFGPVGCYF KTALFETVCF ASILSITTVS VERYVAILHP FRAKLQSTRR RAL RILGIV WGFSVLFSLP NTSIHGIKFH YFPNGSLVPG SATCTVIKPM WIYNFIIQVT SFLFYLLPMT VISVLYYLMA LRLK KDKSL EADEGNANIQ RPCRKSVNKM LFVLVLVFAI CWAPFHIDRL FFSFVEEWSE SLAAVFNLVH VVSGVFFYLS SAVNP IIYN LLSRRFQAAF QNVISSFHKQ WHSQHDPQLP PAQRNIFLTE CHFVELTEDI GPQFPCQSSM HNSHLPAALS SEQMSR TNY QSFHFNKT |
-Experimental details
-Structure determination
Method | cryo EM |
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Processing | single particle reconstruction |
Aggregation state | particle |
-Sample preparation
Buffer | pH: 7.4 |
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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 (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 |
-Image processing
Final reconstruction | Resolution.type: BY AUTHOR / Resolution: 2.8 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 2087642 |
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Initial angle assignment | Type: OTHER |
Final angle assignment | Type: OTHER |