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Open data
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Basic information
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Title | GPR110/G13 complex | |||||||||
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Function / homology | ![]() energy reserve metabolic process / fat cell differentiation / regulation of lipid metabolic process / synapse assembly / G protein-coupled receptor activity / 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 ...energy reserve metabolic process / fat cell differentiation / regulation of lipid metabolic process / synapse assembly / G protein-coupled receptor activity / 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 / adenylate cyclase-activating G protein-coupled receptor signaling pathway / G protein-coupled acetylcholine receptor signaling pathway / G-protein activation / 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 / memory / 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 / neuron projection development / 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 / G alpha (i) signalling events / fibroblast proliferation / cytoplasmic vesicle / G alpha (s) signalling events / G alpha (q) signalling events / Ras protein signal transduction / cell population proliferation / Extra-nuclear estrogen signaling / cell surface receptor signaling pathway / G protein-coupled receptor signaling pathway / lysosomal membrane / GTPase activity / synapse / protein-containing complex binding / signal transduction / extracellular exosome / extracellular region / membrane / plasma membrane / cytosol / cytoplasm Similarity search - Function | |||||||||
Biological species | ![]() | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 2.83 Å | |||||||||
![]() | He Y / Zhu X | |||||||||
Funding support | ![]()
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![]() | ![]() Title: Structural basis of adhesion GPCR GPR110 activation by stalk peptide and G-proteins coupling. Authors: Xinyan Zhu / Yu Qian / Xiaowan Li / Zhenmei Xu / Ruixue Xia / Na Wang / Jiale Liang / Han Yin / Anqi Zhang / Changyou Guo / Guangfu Wang / Yuanzheng He / ![]() Abstract: Adhesion G protein-coupled receptors (aGPCRs) are keys of many physiological events and attractive targets for various diseases. aGPCRs are also known to be capable of self-activation via an ...Adhesion G protein-coupled receptors (aGPCRs) are keys of many physiological events and attractive targets for various diseases. aGPCRs are also known to be capable of self-activation via an autoproteolysis process that removes the inhibitory GAIN domain on the extracellular side of receptor and releases a stalk peptide to bind and activate the transmembrane side of receptor. However, the detailed mechanism of aGPCR activation remains elusive. Here, we report the cryo-electron microscopy structures of GPR110 (ADGRF1), a member of aGPCR, in complex with G, G, G, G and G The structures reveal distinctive ligand engaging model and activation conformations of GPR110. The structures also unveil the rarely explored GPCR/G and GPCR/G engagements. A comparison of G, G, G, G and G engagements with GPR110 reveals details of G-protein engagement, including a dividing point at the far end of the alpha helix 5 (αH5) of Gα subunit that separates G/G engagements from G/G/G engagements. This is also where G/G bind the receptor through both hydrophobic and polar interaction, while G/G/G engage receptor mainly through hydrophobic interaction. We further provide physiological evidence of GPR110 activation via stalk peptide. Taken together, our study fills the missing information of GPCR/G-protein engagement and provides a framework for understanding aGPCR activation and GPR110 signaling. | |||||||||
History |
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Structure visualization
Supplemental images |
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Downloads & links
-EMDB archive
Map data | ![]() | 56 MB | ![]() | |
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Header (meta data) | ![]() ![]() | 16.8 KB 16.8 KB | Display Display | ![]() |
FSC (resolution estimation) | ![]() | 9 KB | Display | ![]() |
Images | ![]() | 75.8 KB | ||
Archive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 7wy0MC ![]() 7wxuC ![]() 7wxwC ![]() 7wz7C ![]() 7x2vC M: atomic model generated by this map C: citing same article ( |
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Similar structure data | Similarity search - Function & homology ![]() |
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Links
EMDB pages | ![]() ![]() |
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Related items in Molecule of the Month |
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Map
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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
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Sample components
-Entire : GPCR/G-protein complex
Entire | Name: GPCR/G-protein complex |
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Components |
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-Supramolecule #1: GPCR/G-protein complex
Supramolecule | Name: GPCR/G-protein complex / type: complex / Chimera: Yes / ID: 1 / Parent: 0 / Macromolecule list: all |
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Source (natural) | Organism: ![]() |
Recombinant expression | Organism: ![]() |
-Macromolecule #1: Engineered G alpha 13 subunit
Macromolecule | Name: Engineered G alpha 13 subunit / type: protein_or_peptide / ID: 1 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() |
Molecular weight | Theoretical: 41.205242 KDa |
Recombinant expression | Organism: ![]() |
Sequence | String: MGCTLSAEDK AAVERSKMID KCLSREKTYV KRLVKILLLG AGESGKSTFL KQMRIIHVNG YSEEECKQYK AVVYSNTIQS IIAIIRAMG RLKIDFGDSA RADDARQLFV LAGAAEEGFM TAELAGVIKR LWKDSGVQAC FNRSREYQLN DSAAYYLNDL D RIAQPNYI ...String: MGCTLSAEDK AAVERSKMID KCLSREKTYV KRLVKILLLG AGESGKSTFL KQMRIIHVNG YSEEECKQYK AVVYSNTIQS IIAIIRAMG RLKIDFGDSA RADDARQLFV LAGAAEEGFM TAELAGVIKR LWKDSGVQAC FNRSREYQLN DSAAYYLNDL D RIAQPNYI PTQQDVLRTR VKTKGIHEYD FEIKNVPFKM VDVGAQRSER KRWFECFDSV TSILFLVSSS EFDQVLMEDR LT NRLTESL NIFETIVNNR VFSNVSIILF LNKTDLLEEK VQIVSIKDYF LEFEGDPHCL RDVQKFLVEC FRNKRRDQQQ KPL YHHFTT SINTENIRLV FRDVKDTILH DNLKQLMLQ |
-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: ![]() |
Molecular weight | Theoretical: 37.915496 KDa |
Recombinant expression | Organism: ![]() |
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: scFv16
Macromolecule | Name: scFv16 / type: protein_or_peptide / ID: 3 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() |
Molecular weight | Theoretical: 26.277299 KDa |
Recombinant expression | Organism: ![]() |
Sequence | String: VQLVESGGGL VQPGGSRKLS CSASGFAFSS FGMHWVRQAP EKGLEWVAYI SSGSGTIYYA DTVKGRFTIS RDDPKNTLFL QMTSLRSED TAMYYCVRSI YYYGSSPFDF WGQGTTLTVS AGGGGSGGGG SGGGGSADIV MTQATSSVPV TPGESVSISC R SSKSLLHS ...String: VQLVESGGGL VQPGGSRKLS CSASGFAFSS FGMHWVRQAP EKGLEWVAYI SSGSGTIYYA DTVKGRFTIS RDDPKNTLFL QMTSLRSED TAMYYCVRSI YYYGSSPFDF WGQGTTLTVS AGGGGSGGGG SGGGGSADIV MTQATSSVPV TPGESVSISC R SSKSLLHS NGNTYLYWFL QRPGQSPQLL IYRMSNLASG VPDRFSGSGS GTAFTLTISR LEAEDVGVYY CMQHLEYPLT FG AGTKLEL |
-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: ![]() |
Molecular weight | Theoretical: 7.861143 KDa |
Recombinant expression | Organism: ![]() |
Sequence | String: MASNNTASIA QARKLVEQLK MEANIDRIKV SKAAADLMAY CEAHAKEDPL LTPVPASENP FREKKFFCAI L |
-Macromolecule #5: Adhesion G-protein coupled receptor F1
Macromolecule | Name: Adhesion G-protein coupled receptor F1 / type: protein_or_peptide / ID: 5 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() |
Molecular weight | Theoretical: 101.465219 KDa |
Recombinant expression | Organism: ![]() |
Sequence | String: MKVGVLWLIS FFTFTDGHGG FLGKNDGIKT KKELIVNKKK HLGPVEEYQL LLQVTYRDSK EKRDLRNFLK LLKPPLLWSH GLIRIIRAK ATTDCNSLNG VLQCTCEDSY TWFPPSCLDP QNCYLHTAGA LPSCECHLNN LSQSVNFCER TKIWGTFKIN E RFTNDLLN ...String: MKVGVLWLIS FFTFTDGHGG FLGKNDGIKT KKELIVNKKK HLGPVEEYQL LLQVTYRDSK EKRDLRNFLK LLKPPLLWSH GLIRIIRAK ATTDCNSLNG VLQCTCEDSY TWFPPSCLDP QNCYLHTAGA LPSCECHLNN LSQSVNFCER TKIWGTFKIN E RFTNDLLN SSSAIYSKYA NGIEIQLKKA YERIQGFESV QVTQFRNGSI VAGYEVVGSS SASELLSAIE HVAEKAKTAL HK LFPLEDG SFRVFGKAQC NDIVFGFGSK DDEYTLPCSS GYRGNITAKC ESSGWQVIRE TCVLSLLEEL NKNFSMIVGN ATE AAVSSF VQNLSVIIRQ NPSTTVGNLA SVVSILSNIS SLSLASHFRV SNSTMEDVIS IADNILNSAS VTNWTVLLRE EKYA SSRLL ETLENISTLV PPTALPLNFS RKFIDWKGIP VNKSQLKRGY SYQIKMCPQN TSIPIRGRVL IGSDQFQRSL PETII SMAS LTLGNILPVS KNGNAQVNGP VISTVIQNYS INEVFLFFSK IESNLSQPHC VFWDFSHLQW NDAGCHLVNE TQDIVT CQC THLTSFSILM SPFVPSTIFP VVKWITYVGL GISIGSLILC LIIEALFWKQ IKKSQTSHTR RICMVNIALS LLIADVW FI VGATVDTTVN PSGVCTAAVF FTHFFYLSLF FWMLMLGILL AYRIILVFHH MAQHLMMAVG FCLGYGCPLI ISVITIAV T QPSNTYKRKD VCWLNWSNGS KPLLAFVVPA LAIVAVNFVV VLLVLTKLWR PTVGERLSRD DKATIIRVGK SLLILTPLL GLTWGFGIGT IVDSQNLAWH VIFALLNAFQ GFFILCFGIL LDSKLRQLLF NKLSALSSWK QTEKQNSSDL SAKPKFSKPF NPLQNKGHY AFSHTGDSSD NIMLTQFVSN E |
-Experimental details
-Structure determination
Method | cryo EM |
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![]() | single particle reconstruction |
Aggregation state | 3D array |
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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: 60.0 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: ![]() |
Electron optics | Illumination mode: OTHER / Imaging mode: BRIGHT FIELD / Nominal defocus max: 2.3000000000000003 µm / Nominal defocus min: 1.2 µm |
Experimental equipment | ![]() Model: Titan Krios / Image courtesy: FEI Company |