+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-60096 | |||||||||
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Title | Human GPR103 -Gq complex bound to QRFP26 | |||||||||
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Sample |
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Keywords | GPCR / MEMBRANE PROTEIN / MEMBRANE PROTEIN-IMMUNE SYSTEM complex | |||||||||
Function / homology | Function and homology information orexigenic neuropeptide QRFP receptor binding / neuropeptide Y receptor activity / Orexin and neuropeptides FF and QRFP bind to their respective receptors / negative regulation of adenylate cyclase-activating adrenergic receptor signaling pathway involved in heart process / regulation of feeding behavior / sensory perception of chemical stimulus / G protein-coupled adenosine receptor signaling pathway / negative regulation of calcium ion-dependent exocytosis / grooming behavior / mu-type opioid receptor binding ...orexigenic neuropeptide QRFP receptor binding / neuropeptide Y receptor activity / Orexin and neuropeptides FF and QRFP bind to their respective receptors / negative regulation of adenylate cyclase-activating adrenergic receptor signaling pathway involved in heart process / regulation of feeding behavior / sensory perception of chemical stimulus / G protein-coupled adenosine receptor signaling pathway / negative regulation of calcium ion-dependent exocytosis / grooming behavior / mu-type opioid receptor binding / positive regulation of urine volume / corticotropin-releasing hormone receptor 1 binding / positive regulation of blood pressure / negative regulation of adenylate cyclase activity / neuropeptide hormone activity / G-protein activation / Activation of the phototransduction cascade / Glucagon-type ligand receptors / Thromboxane signalling through TP receptor / Sensory perception of sweet, bitter, and umami (glutamate) taste / G beta:gamma signalling through PI3Kgamma / G beta:gamma signalling through CDC42 / Cooperation of PDCL (PhLP1) and TRiC/CCT in G-protein beta folding / positive regulation of neural precursor cell proliferation / Activation of G protein gated Potassium channels / Inhibition of voltage gated Ca2+ channels via Gbeta/gamma subunits / Ca2+ pathway / G alpha (z) signalling events / Vasopressin regulates renal water homeostasis via Aquaporins / Glucagon-like Peptide-1 (GLP1) regulates insulin secretion / Adrenaline,noradrenaline inhibits insulin secretion / ADP signalling through P2Y purinoceptor 12 / G alpha (q) signalling events / gamma-aminobutyric acid signaling pathway / negative regulation of synaptic transmission / Thrombin signalling through proteinase activated receptors (PARs) / G alpha (i) signalling events / alkylglycerophosphoethanolamine phosphodiesterase activity / Activation of G protein gated Potassium channels / G-protein activation / G beta:gamma signalling through PI3Kgamma / Prostacyclin signalling through prostacyclin receptor / G beta:gamma signalling through PLC beta / ADP signalling through P2Y purinoceptor 1 / Thromboxane signalling through TP receptor / Presynaptic function of Kainate receptors / G beta:gamma signalling through CDC42 / Inhibition of voltage gated Ca2+ channels via Gbeta/gamma subunits / Glucagon-type ligand receptors / G alpha (12/13) signalling events / G beta:gamma signalling through BTK / ADP signalling through P2Y purinoceptor 12 / Adrenaline,noradrenaline inhibits insulin secretion / beta-2 adrenergic receptor binding / Cooperation of PDCL (PhLP1) and TRiC/CCT in G-protein beta folding / Thrombin signalling through proteinase activated receptors (PARs) / Ca2+ pathway / Extra-nuclear estrogen signaling / G alpha (z) signalling events / G alpha (s) signalling events / G alpha (q) signalling events / photoreceptor outer segment membrane / G alpha (i) signalling events / spectrin binding / Glucagon-like Peptide-1 (GLP1) regulates insulin secretion / Vasopressin regulates renal water homeostasis via Aquaporins / neuronal dense core vesicle / PKA activation in glucagon signalling / regulation of calcium ion transport / negative regulation of apoptotic signaling pathway / neuropeptide signaling pathway / developmental growth / photoreceptor outer segment / D1 dopamine receptor binding / Hedgehog 'off' state / Adenylate cyclase inhibitory pathway / positive regulation of insulin receptor signaling pathway / cellular response to hormone stimulus / cardiac muscle cell apoptotic process / positive regulation of vascular associated smooth muscle cell proliferation / insulin-like growth factor receptor binding / adenylate cyclase activator activity / ionotropic glutamate receptor binding / photoreceptor inner segment / adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway / response to nutrient / positive regulation of superoxide anion generation / locomotory behavior / Regulation of insulin secretion / G protein-coupled receptor binding / G protein-coupled receptor activity / peptide binding / bone development / G-protein beta/gamma-subunit complex binding / adenylate cyclase-activating 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 / platelet aggregation Similarity search - Function | |||||||||
Biological species | Homo sapiens (human) / Lama glama (llama) / Rattus norvegicus (Norway rat) / Bos taurus (cattle) / Mus musculus (house mouse) | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 3.19 Å | |||||||||
Authors | Iwama A / Akasaka H / Sano FK / Oshima HS / Shihoya W / Nureki O | |||||||||
Funding support | Japan, 1 items
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Citation | Journal: Nat Commun / Year: 2024 Title: Structure and dynamics of the pyroglutamylated RF-amide peptide QRFP receptor GPR103. Authors: Aika Iwama / Ryoji Kise / Hiroaki Akasaka / Fumiya K Sano / Hidetaka S Oshima / Asuka Inoue / Wataru Shihoya / Osamu Nureki / Abstract: Pyroglutamylated RF-amide peptide (QRFP) is a peptide hormone with a C-terminal RF-amide motif. QRFP selectively activates a class A G-protein-coupled receptor (GPCR) GPR103 to exert various ...Pyroglutamylated RF-amide peptide (QRFP) is a peptide hormone with a C-terminal RF-amide motif. QRFP selectively activates a class A G-protein-coupled receptor (GPCR) GPR103 to exert various physiological functions such as energy metabolism and appetite regulation. Here, we report the cryo-electron microscopy structure of the QRFP26-GPR103-G complex at 3.19 Å resolution. QRFP26 adopts an extended structure bearing no secondary structure, with its N-terminal and C-terminal sides recognized by extracellular and transmembrane domains of GPR103 respectively. This movement, reminiscent of class B1 GPCRs except for orientation and structure of the ligand, is critical for the high-affinity binding and receptor specificity of QRFP26. Mutagenesis experiments validate the functional importance of the binding mode of QRFP26 by GPR103. Structural comparisons with closely related receptors, including RY-amide peptide-recognizing GPCRs, revealed conserved and diversified peptide recognition mechanisms, providing profound insights into the biological significance of RF-amide peptides. Collectively, this study not only advances our understanding of GPCR-ligand interactions, but also paves the way for the development of novel therapeutics targeting metabolic and appetite disorders and emergency medical care. | |||||||||
History |
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-Structure visualization
Supplemental images |
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-Downloads & links
-EMDB archive
Map data | emd_60096.map.gz | 33.9 MB | EMDB map data format | |
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Header (meta data) | emd-60096-v30.xml emd-60096.xml | 20.7 KB 20.7 KB | Display Display | EMDB header |
Images | emd_60096.png | 76 KB | ||
Filedesc metadata | emd-60096.cif.gz | 6.7 KB | ||
Others | emd_60096_half_map_1.map.gz emd_60096_half_map_2.map.gz | 32.4 MB 32.4 MB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-60096 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-60096 | HTTPS FTP |
-Validation report
Summary document | emd_60096_validation.pdf.gz | 708 KB | Display | EMDB validaton report |
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Full document | emd_60096_full_validation.pdf.gz | 707.6 KB | Display | |
Data in XML | emd_60096_validation.xml.gz | 12.8 KB | Display | |
Data in CIF | emd_60096_validation.cif.gz | 15 KB | Display | |
Arichive directory | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-60096 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-60096 | HTTPS FTP |
-Related structure data
Related structure data | 8zh8MC 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_60096.map.gz / Format: CCP4 / Size: 67 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: 1.0215 Å | ||||||||||||||||||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||
Details | EMDB XML:
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-Supplemental data
-Half map: #2
File | emd_60096_half_map_1.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Half map: #1
File | emd_60096_half_map_2.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Sample components
-Entire : Human GPR103 -Gq complex bound to QRFP26
Entire | Name: Human GPR103 -Gq complex bound to QRFP26 |
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Components |
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-Supramolecule #1: Human GPR103 -Gq complex bound to QRFP26
Supramolecule | Name: Human GPR103 -Gq complex bound to QRFP26 / type: complex / ID: 1 / Parent: 0 / Macromolecule list: all |
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Source (natural) | Organism: Homo sapiens (human) |
-Macromolecule #1: Pyroglutamylated RF-amide peptide receptor
Macromolecule | Name: Pyroglutamylated RF-amide peptide receptor / 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: 45.652039 KDa |
Recombinant expression | Organism: Homo sapiens (human) |
Sequence | String: MKTIIALSYI FCLVFADYKD DDDKQALNIT PEQFSRLLRD HNLTREQFIA LYRLRPLVYT PELPGRAKLA LVLTGVLIFA LALFGNALV FYVVTRSKAM RTVTNIFICS LALSDLLITF FCIPVTMLQN ISDNWLGGAF ICKMVPFVQS TAVVTEILTM T CIAVERHQ ...String: MKTIIALSYI FCLVFADYKD DDDKQALNIT PEQFSRLLRD HNLTREQFIA LYRLRPLVYT PELPGRAKLA LVLTGVLIFA LALFGNALV FYVVTRSKAM RTVTNIFICS LALSDLLITF FCIPVTMLQN ISDNWLGGAF ICKMVPFVQS TAVVTEILTM T CIAVERHQ GLVHPFKMKW QYTNRRAFTM LGVVWLVAVI VGSPMWHVQQ LEIKYDFLYE KEHICCLEEW TSPVHQKIYT TF ILVILFL LPLMVMLILY SKIGYELWIK KRVGDGSVLR TIHGKEMSKI ARKKKRAVIM MVTVVALFAV CWAPFHVVHM MIE YSNFEK EYDDVTIKMI FAIVQIIGFS NSICNPIVYA FMNENFKKNV LSAVCYCIVN KTFSPAQRHG NSGSGGGGSG GSSS GG UniProtKB: Pyroglutamylated RF-amide peptide receptor |
-Macromolecule #2: nanobody Nb35
Macromolecule | Name: nanobody Nb35 / type: protein_or_peptide / ID: 2 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: Lama glama (llama) |
Molecular weight | Theoretical: 15.015728 KDa |
Recombinant expression | Organism: Escherichia coli (E. coli) |
Sequence | String: MGQVQLQESG GGLVQPGGSL RLSCAASGFT FSNYKMNWVR QAPGKGLEWV SDISQSGASI SYTGSVKGRF TISRDNAKNT LYLQMNSLK PEDTAVYYCA RCPAPFTRDC FDVTSTTYAY RGQGTQVTVS SLHHHHHH |
-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: Rattus norvegicus (Norway rat) |
Molecular weight | Theoretical: 38.744371 KDa |
Recombinant expression | Organism: Homo sapiens (human) |
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 UniProtKB: Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1 |
-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: Bos taurus (cattle) |
Molecular weight | Theoretical: 7.547685 KDa |
Recombinant expression | Organism: Homo sapiens (human) |
Sequence | String: MASNNTASIA QARKLVEQLK MEANIDRIKV SKAAADLMAY CEAHAKEDPL LTPVPASENP FREKKFFS UniProtKB: Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2 |
-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,Guanine nucleotide-binding protein G(i) subunit alpha-2,Guanine nucleotide-binding protein G(s) subunit alpha isoforms XLas 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: 36.573531 KDa |
Recombinant expression | Organism: Homo sapiens (human) |
Sequence | String: MASNNTASIA QARKLVEQLK MEANIDRIKV SKAAADLMAY CEAHAKEDPL LTPVPASENP FREKKFFCAI LGSAGSAGSA MGSTVSAED KAAAERSKMI DKNLREDGEK ARRTLRLLLL GADNSGKSTI VKQMRILHGG SGGSGGTSGI FETKFQVDKV N FHMFDVGG ...String: MASNNTASIA QARKLVEQLK MEANIDRIKV SKAAADLMAY CEAHAKEDPL LTPVPASENP FREKKFFCAI LGSAGSAGSA MGSTVSAED KAAAERSKMI DKNLREDGEK ARRTLRLLLL GADNSGKSTI VKQMRILHGG SGGSGGTSGI FETKFQVDKV N FHMFDVGG QRDERRKWIQ CFNDVTAIIF VVDSSDYNRL QEALNDFKSI WNNRWLRTIS VILFLNKQDL LAEKVLAGKS KI EDYFPEF ARYTTPEDAT PEPGEDPRVT RAKYFIRKEF VDISTASGDG RHICYPHFTC AVDTENARRI FNDCKDIILQ MNL REYNLV UniProtKB: Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2, Guanine nucleotide-binding protein G(i) subunit alpha-2, Guanine nucleotide-binding protein G(s) subunit alpha isoforms XLas |
-Macromolecule #6: scFv16
Macromolecule | Name: scFv16 / type: protein_or_peptide / ID: 6 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: Mus musculus (house mouse) |
Molecular weight | Theoretical: 27.720795 KDa |
Recombinant expression | Organism: Spodoptera frugiperda (fall armyworm) |
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 KAAAASSEDL YFQ |
-Macromolecule #7: QRF-amide
Macromolecule | Name: QRF-amide / type: protein_or_peptide / ID: 7 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: Homo sapiens (human) |
Molecular weight | Theoretical: 2.835161 KDa |
Sequence | String: TSGPLGNLAE ELNGYSRKKG GFSFRF(NH2) UniProtKB: Orexigenic neuropeptide QRFP |
-Experimental details
-Structure determination
Method | cryo EM |
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Processing | single particle reconstruction |
Aggregation state | particle |
-Sample preparation
Buffer | pH: 8 |
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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: 0.83 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: 1.6 µm / Nominal defocus min: 0.8 µm |
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |
-Image processing
Startup model | Type of model: NONE |
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Final reconstruction | Resolution.type: BY AUTHOR / Resolution: 3.19 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 142831 |
Initial angle assignment | Type: RANDOM ASSIGNMENT |
Final angle assignment | Type: MAXIMUM LIKELIHOOD |