+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-32890 | |||||||||
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Title | ADGRL3/Gi complex | |||||||||
Map data | ||||||||||
Sample |
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Function / homology | Function and homology information locomotion involved in locomotory behavior / cell-cell adhesion via plasma-membrane adhesion molecules / maintenance of postsynaptic specialization structure / positive regulation of synapse assembly / Adenylate cyclase inhibitory pathway / positive regulation of protein localization to cell cortex / regulation of cAMP-mediated signaling / D2 dopamine receptor binding / G protein-coupled serotonin receptor binding / regulation of mitotic spindle organization ...locomotion involved in locomotory behavior / cell-cell adhesion via plasma-membrane adhesion molecules / maintenance of postsynaptic specialization structure / positive regulation of synapse assembly / Adenylate cyclase inhibitory pathway / positive regulation of protein localization to cell cortex / regulation of cAMP-mediated signaling / D2 dopamine receptor binding / G protein-coupled serotonin receptor binding / regulation of mitotic spindle organization / cellular response to forskolin / synapse assembly / adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway / response to cocaine / Regulation of insulin secretion / G protein-coupled receptor binding / G protein-coupled receptor activity / synapse organization / neuron migration / G-protein beta/gamma-subunit complex binding / Olfactory Signaling Pathway / Activation of the phototransduction cascade / adenylate cyclase-modulating G protein-coupled receptor signaling pathway / G beta:gamma signalling through PLC beta / Presynaptic function of Kainate receptors / Schaffer collateral - CA1 synapse / 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 / response to peptide hormone / 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 / GDP binding / G-protein beta-subunit binding / Inactivation, recovery and regulation of the phototransduction cascade / heterotrimeric G-protein complex / G alpha (12/13) signalling events / cell-cell junction / 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 / cell cortex / midbody / G alpha (i) signalling events / fibroblast proliferation / G alpha (s) signalling events / carbohydrate binding / G alpha (q) signalling events / Ras protein signal transduction / postsynaptic membrane / Extra-nuclear estrogen signaling / cell population proliferation / cell surface receptor signaling pathway / G protein-coupled receptor signaling pathway / cell division / axon / lysosomal membrane / GTPase activity / centrosome / glutamatergic synapse / synapse / calcium ion binding / protein-containing complex binding / nucleolus / GTP binding / magnesium ion binding / signal transduction / extracellular exosome / nucleoplasm / membrane / plasma membrane / cytoplasm / cytosol Similarity search - Function | |||||||||
Biological species | Homo sapiens (human) / Mus musculus (house mouse) | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 2.97 Å | |||||||||
Authors | He Y / Qian Y | |||||||||
Funding support | China, 1 items
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Citation | Journal: Mol Cell / Year: 2022 Title: Structural insights into adhesion GPCR ADGRL3 activation and G, G, G, and G coupling. Authors: Yu Qian / Zhengxiong Ma / Chunhong Liu / Xinzhi Li / Xinyan Zhu / Na Wang / Zhenmei Xu / Ruixue Xia / Jiale Liang / Yaning Duan / Han Yin / Yangjie Xiong / Anqi Zhang / Changyou Guo / Zheng ...Authors: Yu Qian / Zhengxiong Ma / Chunhong Liu / Xinzhi Li / Xinyan Zhu / Na Wang / Zhenmei Xu / Ruixue Xia / Jiale Liang / Yaning Duan / Han Yin / Yangjie Xiong / Anqi Zhang / Changyou Guo / Zheng Chen / Zhiwei Huang / Yuanzheng He / Abstract: Adhesion G-protein-coupled receptors (aGPCRs) play key roles in a diversity of physiologies. A hallmark of aGPCR activation is the removal of the inhibitory GAIN domain and the dipping of the cleaved ...Adhesion G-protein-coupled receptors (aGPCRs) play key roles in a diversity of physiologies. A hallmark of aGPCR activation is the removal of the inhibitory GAIN domain and the dipping of the cleaved stalk peptide into the ligand-binding pocket of receptors; however, the detailed mechanism remains obscure. Here, we present cryoelectron microscopy (cryo-EM) structures of ADGRL3 in complex with G, G, G, and G. The structures reveal unique ligand-engaging mode, distinctive activation conformation, and key mechanisms of aGPCR activation. The structures also reveal the uncharted structural information of GPCR/G coupling. A comparison of G, G, G, and G engagements with ADGRL3 reveals the key determinant of G-protein coupling on the far end of αH5 of Gα. A detailed analysis of the engagements allows us to design mutations that specifically enhance one pathway over others. Taken together, our study lays the groundwork for understanding aGPCR activation and G-protein-coupling selectivity. | |||||||||
History |
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-Structure visualization
Supplemental images |
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-Downloads & links
-EMDB archive
Map data | emd_32890.map.gz | 56.1 MB | EMDB map data format | |
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Header (meta data) | emd-32890-v30.xml emd-32890.xml | 17.8 KB 17.8 KB | Display Display | EMDB header |
FSC (resolution estimation) | emd_32890_fsc.xml | 9.1 KB | Display | FSC data file |
Images | emd_32890.png | 73.3 KB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-32890 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-32890 | HTTPS FTP |
-Related structure data
Related structure data | 7wybMC 7wy5C 7wy8C 7x10C 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_32890.map.gz / Format: CCP4 / Size: 64 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||
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Voxel size | X=Y=Z: 1.1 Å | ||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||
Details | EMDB XML:
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-Supplemental data
-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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-Supramolecule #2: GPCR/G-protein complex
Supramolecule | Name: GPCR/G-protein complex / type: complex / Chimera: Yes / ID: 2 / Parent: 1 / Macromolecule list: #1-#4 |
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Source (natural) | Organism: Homo sapiens (human) |
-Supramolecule #3: ADGRL3
Supramolecule | Name: ADGRL3 / type: complex / Chimera: Yes / ID: 3 / Parent: 1 / Macromolecule list: #5 |
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Source (natural) | Organism: Mus musculus (house mouse) |
-Macromolecule #1: 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: 1 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: Homo sapiens (human) |
Molecular weight | Theoretical: 40.414047 KDa |
Recombinant expression | Organism: Insect BA phytoplasma (bacteria) |
Sequence | String: MGCTLSAEDK AAVERSKMID RNLREDGEKA AREVKLLLLG AGESGKNTIV KQMKIIHEAG YSEEECKQYK AVVYSNTIQS IIAIIRAMG RLKIDFGDSA RADDARQLFV LAGAAEEGFM TAELAGVIKR LWKDSGVQAC FNRSREYQLN DSAAYYLNDL D RIAQPNYI ...String: MGCTLSAEDK AAVERSKMID RNLREDGEKA AREVKLLLLG AGESGKNTIV KQMKIIHEAG YSEEECKQYK AVVYSNTIQS IIAIIRAMG RLKIDFGDSA RADDARQLFV LAGAAEEGFM TAELAGVIKR LWKDSGVQAC FNRSREYQLN DSAAYYLNDL D RIAQPNYI PTQQDVLRTR VKTTGIVETH FTFKDLHFKM FDVGAQRSER KKWIHCFEGV TAIIFCVALS DYDLVLAEDE EM NRMHASM KLFDSICNNK WFTDTSIILF LNKKDLFEEK IKKSPLTICY PEYAGSNTYE EAAAYIQCQF EDLNKRKDTK EIY THFTCS TDTKNVQFVF DAVTDVIIKN NLKDCGLF |
-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: Insect BA phytoplasma (bacteria) |
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: 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: 3 / 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: Insect BA phytoplasma (bacteria) |
Sequence | String: MASNNTASIA QARKLVEQLK MEANIDRIKV SKAAADLMAY CEAHAKEDPL LTPVPASENP FREKKFFCAI L |
-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: 26.277299 KDa |
Recombinant expression | Organism: Insect BA phytoplasma (bacteria) |
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 #5: Isoform 3 of Adhesion G protein-coupled receptor L3
Macromolecule | Name: Isoform 3 of Adhesion G protein-coupled receptor L3 / type: protein_or_peptide / ID: 5 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: Mus musculus (house mouse) |
Molecular weight | Theoretical: 172.044625 KDa |
Recombinant expression | Organism: Insect BA phytoplasma (bacteria) |
Sequence | String: MWPPQLLILT MLLAPVVHGG KHNERHPALA APLRHAERSP GGALPPRHLL QQPAAERSTA HRGQGPRGAA RGVRGPGAPG AQIAAQAFS RAPIPMAVVR RELSCESYPI ELRCPGTDVI MIESANYGRT DDKICDSDPA QMENIRCYLP DAYKIMSQRC N NRTQCAVV ...String: MWPPQLLILT MLLAPVVHGG KHNERHPALA APLRHAERSP GGALPPRHLL QQPAAERSTA HRGQGPRGAA RGVRGPGAPG AQIAAQAFS RAPIPMAVVR RELSCESYPI ELRCPGTDVI MIESANYGRT DDKICDSDPA QMENIRCYLP DAYKIMSQRC N NRTQCAVV AGPDVFPDPC PGTYKYLEVQ YECVPYKVEQ KVFLCPGLLK GVYQSEHLFE SDHQSGAWCK DPLQASDKIY YM PWTPYRT DTLTEYSSKD DFIAGRPTTT YKLPHRVDGT GFVVYDGALF FNKERTRNIV KFDLRTRIKS GEAIIANANY HDT SPYRWG GKSDIDLAVD ENGLWVIYAT EQNNGKIVIS QLNPYTLRIE GTWDTAYDKR SASNAFMICG ILYVVKSVYE DDDN EATGN KIDYIYNTDQ SKDSLVDVPF PNSYQYIAAV DYNPRDNLLY VWNNYHVVKY SLDFGPLDSR SGPVHHGQVS YISPP IHLD SELERPPVRG ISTTGSLGMG STTTSTTLRT TTWNIGRSTT ASLPGRRNRS TSTPSPAVEV LDDVTTHLPS AASQIP AME ESCEAVEARE IMWFKTRQGQ VAKQPCPAGT IGVSTYLCLA PDGIWDPQGP DLSNCSSPWV NHITQKLKSG ETAANIA RE LAEQTRNHLN AGDITYSVRA MDQLVGLLDV QLRNLTPGGK DSAARSLNKL QKRERSCRAY VQAMVETVNN LLQPQALN A WRDLTTSDQL RAATMLLDTV EESAFVLADN LLKTDIVREN TDNIQLEVAR LSTEGNLEDL KFPENMGHGS TIQLSANTL KQNGRNGEIR VAFVLYNNLG PYLSTENASM KLGTEAMSTN HSVIVNSPVI TAAINKEFSN KVYLADPVVF TVKHIKQSEE NFNPNCSFW SYSKRTMTGY WSTQGCRLLT TNKTHTTCSC NHLTNFAVLM AHVEVKHSDA VHDLLLDVIT WVGILLSLVC L LICIFTFC FFRGLQSDRN TIHKNLCISL FVAELLFLIG INRTDQPIAC AVFAALLHFF FLAAFTWMFL EGVQLYIMLV EV FESEHSR RKYFYLVGYG MPALIVAVSA AVDYRSYGTD KVCWLRLDTY FIWSFIGPAT LIIMLNVIFL GIALYKMFHH TAI LKPESG CLDNINYEDN RPFIKSWVIG AIALLCLLGL TWAFGLMYIN ESTVIMAYLF TIFNSLQGMF IFIFHCVLQK KVRK EYGKC LRTHCCSGKS TESSIGSGKT SGSRTPGRYS TGSQSRIRRM WNDTVRKQSE SSFITGDINS SASLNREPYR ETKGL LNNA RDTSVMDTLP LNGNHGNSYS IAGGEYLSNC VQIIDRGYNH NETALEKKIL KELTSNYIPS YLNNHERSSE QNRNMM NKL VNNLGSGSED DAIVLDDAAS FNHEESLGLE LIHEESDAPL LPPRVYSTDN HQPHHYSRRR FPQDHSESFF PLLTDEH TE DLQSPHRDSL YTSMPALAGV PAADSVTTST QTEAAAAKGG DAEDVYYKSM PNLGSRNHVH PLHAYYQLGR GSSDGFIV P PNKDGASPEG TSKGPAHLVT SL |
-Experimental details
-Structure determination
Method | cryo EM |
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Processing | single particle reconstruction |
Aggregation state | 3D array |
-Sample preparation
Buffer | pH: 7.5 |
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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 K2 SUMMIT (4k x 4k) / Average electron dose: 60.0 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN |
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 |