+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-32884 | |||||||||
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Title | ADGRL3/Gq 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 / synapse assembly / response to cocaine / G protein-coupled receptor activity / adenylate cyclase-activating G protein-coupled receptor signaling pathway / synapse organization / neuron migration ...locomotion involved in locomotory behavior / cell-cell adhesion via plasma-membrane adhesion molecules / maintenance of postsynaptic specialization structure / positive regulation of synapse assembly / synapse assembly / response to cocaine / G protein-coupled receptor activity / adenylate cyclase-activating G protein-coupled receptor signaling pathway / synapse organization / neuron migration / Olfactory Signaling Pathway / Schaffer collateral - CA1 synapse / Activation of the phototransduction cascade / Prostacyclin signalling through prostacyclin receptor / G beta:gamma signalling through PLC beta / Presynaptic function of Kainate receptors / Thromboxane signalling through TP receptor / Glucagon signaling in metabolic regulation / 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 / G beta:gamma signalling through CDC42 / Vasopressin regulates renal water homeostasis via Aquaporins / G beta:gamma signalling through BTK / ADP signalling through P2Y purinoceptor 12 / Synthesis, secretion, and inactivation of Glucagon-like Peptide-1 (GLP-1) / Glucagon-type ligand receptors / Sensory perception of sweet, bitter, and umami (glutamate) taste / photoreceptor disc membrane / G alpha (z) signalling events / Adrenaline,noradrenaline inhibits insulin secretion / Glucagon-like Peptide-1 (GLP1) regulates insulin secretion / ADORA2B mediated anti-inflammatory cytokines production / cellular response to catecholamine stimulus / sensory perception of taste / ADP signalling through P2Y purinoceptor 1 / adenylate cyclase-activating dopamine receptor signaling pathway / G beta:gamma signalling through PI3Kgamma / GPER1 signaling / cellular response to prostaglandin E stimulus / Cooperation of PDCL (PhLP1) and TRiC/CCT in G-protein beta folding / Inactivation, recovery and regulation of the phototransduction cascade / G-protein beta-subunit binding / heterotrimeric G-protein complex / cell-cell junction / 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 / carbohydrate binding / G alpha (s) signalling events / G alpha (q) signalling events / postsynaptic membrane / Ras protein signal transduction / cell population proliferation / Extra-nuclear estrogen signaling / cell surface receptor signaling pathway / G protein-coupled receptor signaling pathway / lysosomal membrane / axon / GTPase activity / glutamatergic synapse / calcium ion binding / synapse / protein-containing complex binding / signal transduction / extracellular exosome / membrane / plasma membrane / cytosol / cytoplasm Similarity search - Function | |||||||||
Biological species | Homo sapiens (human) / Mus musculus (house mouse) | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 2.83 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_32884.map.gz | 55.8 MB | EMDB map data format | |
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Header (meta data) | emd-32884-v30.xml emd-32884.xml | 16.3 KB 16.3 KB | Display Display | EMDB header |
FSC (resolution estimation) | emd_32884_fsc.xml | 9.1 KB | Display | FSC data file |
Images | emd_32884.png | 73.1 KB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-32884 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-32884 | HTTPS FTP |
-Validation report
Summary document | emd_32884_validation.pdf.gz | 347 KB | Display | EMDB validaton report |
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Full document | emd_32884_full_validation.pdf.gz | 346.6 KB | Display | |
Data in XML | emd_32884_validation.xml.gz | 10.8 KB | Display | |
Data in CIF | emd_32884_validation.cif.gz | 14.2 KB | Display | |
Arichive directory | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-32884 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-32884 | HTTPS FTP |
-Related structure data
Related structure data | 7wy5MC 7wy8C 7wybC 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_32884.map.gz / Format: CCP4 / Size: 64 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: 1.1 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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Source (natural) | Organism: Homo sapiens (human) |
-Macromolecule #1: engineered mini G alpha q subunit
Macromolecule | Name: engineered mini G alpha q subunit / 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: 41.855578 KDa |
Recombinant expression | Organism: Insect BA phytoplasma (bacteria) |
Sequence | String: MMGCTLSAED KAAVERSKMI EKQLQKDKQV YRRTLRLLLL GADNSGKSTI VKQMRIYHVN GYSEEECKQY KAVVYSNTIQ SIIAIIRAM GRLKIDFGDS ARADDARQLF VLAGAAEEGF MTAELAGVIK RLWKDSGVQA CFNRSREYQL NDSAAYYLND L DRIAQPNY ...String: MMGCTLSAED KAAVERSKMI EKQLQKDKQV YRRTLRLLLL GADNSGKSTI VKQMRIYHVN GYSEEECKQY KAVVYSNTIQ SIIAIIRAM GRLKIDFGDS ARADDARQLF VLAGAAEEGF MTAELAGVIK RLWKDSGVQA CFNRSREYQL NDSAAYYLND L DRIAQPNY IPTQQDVLRT RVKTSGIFET KFQVDKVNFH MFDVGAQRDE RRKWIQCFND VTAIIFVVDS SDYNRLQEAL ND FKSIWNN RWLRTISVIL FLNKQDLLAE KVLAGKSKIE DYFPEFARYT TPEDATPEPG EDPRVTRAKY FIRKEFVDIS TAS GDGRHI CYPHFTCSVD TENARRIFND CKDIILQMNL REYNLV |
-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: NB35
Macromolecule | Name: NB35 / 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: 17.381584 KDa |
Recombinant expression | Organism: Insect BA phytoplasma (bacteria) |
Sequence | String: MKYLLPTAAA GLLLLAAQPA MAQVQLQESG GGLVQPGGSL RLSCAASGFT FSNYKMNWVR QAPGKGLEWV SDISQSGASI SYTGSVKGR FTISRDNAKN TLYLQMNSLK PEDTAVYYCA RCPAPFTRDC FDVTSTTYAY RGQGTQVTVS SAAALEHHHH H H |
-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 |