+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-29684 | |||||||||
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Title | Cryo-EM structure of ADGRF1 coupled to miniGs/q | |||||||||
Map data | ||||||||||
Sample |
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Keywords | GPCR / agonist / G protein / signaling / SIGNALING PROTEIN | |||||||||
Function / homology | Function and homology information G protein-coupled receptor activity / Olfactory Signaling Pathway / 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 ...G protein-coupled receptor activity / Olfactory Signaling Pathway / 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 / Cooperation of PDCL (PhLP1) and TRiC/CCT in G-protein beta folding / cellular response to prostaglandin E stimulus / Inactivation, recovery and regulation of the phototransduction cascade / G-protein beta-subunit binding / 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 / Ca2+ pathway / phospholipase C-activating G protein-coupled receptor signaling pathway / G alpha (i) signalling events / fibroblast proliferation / 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 / membrane / plasma membrane / cytosol / cytoplasm Similarity search - Function | |||||||||
Biological species | Homo sapiens (human) / Lama glama (llama) | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 3.44 Å | |||||||||
Authors | Jones D / Rawson S / Blacklow S | |||||||||
Funding support | United States, 1 items
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Citation | Journal: Nat Commun / Year: 2023 Title: Tethered agonist activated ADGRF1 structure and signalling analysis reveal basis for G protein coupling. Authors: Daniel T D Jones / Andrew N Dates / Shaun D Rawson / Maggie M Burruss / Colin H Lipper / Stephen C Blacklow / Abstract: Adhesion G Protein Coupled Receptors (aGPCRs) have evolved an activation mechanism to translate extracellular force into liberation of a tethered agonist (TA) to effect cell signalling. We report ...Adhesion G Protein Coupled Receptors (aGPCRs) have evolved an activation mechanism to translate extracellular force into liberation of a tethered agonist (TA) to effect cell signalling. We report here that ADGRF1 can signal through all major G protein classes and identify the structural basis for a previously reported Gα preference by cryo-EM. Our structure shows that Gα preference in ADGRF1 may derive from tighter packing at the conserved F569 of the TA, altering contacts between TM helix I and VII, with a concurrent rearrangement of TM helix VII and helix VIII at the site of Gα recruitment. Mutational studies of the interface and of contact residues within the 7TM domain identify residues critical for signalling, and suggest that Gα signalling is more sensitive to mutation of TA or binding site residues than Gα. Our work advances the detailed molecular understanding of aGPCR TA activation, identifying features that potentially explain preferential signal modulation. | |||||||||
History |
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-Structure visualization
Supplemental images |
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-Downloads & links
-EMDB archive
Map data | emd_29684.map.gz | 118 MB | EMDB map data format | |
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Header (meta data) | emd-29684-v30.xml emd-29684.xml | 22.7 KB 22.7 KB | Display Display | EMDB header |
FSC (resolution estimation) | emd_29684_fsc.xml | 10.6 KB | Display | FSC data file |
Images | emd_29684.png | 53.7 KB | ||
Filedesc metadata | emd-29684.cif.gz | 6.6 KB | ||
Others | emd_29684_additional_1.map.gz emd_29684_additional_2.map.gz emd_29684_half_map_1.map.gz emd_29684_half_map_2.map.gz | 2.8 MB 109.4 MB 116 MB 116 MB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-29684 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-29684 | HTTPS FTP |
-Validation report
Summary document | emd_29684_validation.pdf.gz | 1.2 MB | Display | EMDB validaton report |
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Full document | emd_29684_full_validation.pdf.gz | 1.2 MB | Display | |
Data in XML | emd_29684_validation.xml.gz | 19.1 KB | Display | |
Data in CIF | emd_29684_validation.cif.gz | 24.7 KB | Display | |
Arichive directory | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-29684 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-29684 | HTTPS FTP |
-Related structure data
Related structure data | 8g2yMC 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_29684.map.gz / Format: CCP4 / Size: 125 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: 0.825 Å | ||||||||||||||||||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||
Details | EMDB XML:
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-Supplemental data
-Additional map: #2
File | emd_29684_additional_1.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Additional map: #1
File | emd_29684_additional_2.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Half map: #2
File | emd_29684_half_map_1.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Half map: #1
File | emd_29684_half_map_2.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Sample components
-Entire : Tethered agonist activated adhesion GPCR ADGRF1 coupled to miniGs/q
Entire | Name: Tethered agonist activated adhesion GPCR ADGRF1 coupled to miniGs/q |
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Components |
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-Supramolecule #1: Tethered agonist activated adhesion GPCR ADGRF1 coupled to miniGs/q
Supramolecule | Name: Tethered agonist activated adhesion GPCR ADGRF1 coupled to miniGs/q type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1-#5 |
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Source (natural) | Organism: Homo sapiens (human) |
-Macromolecule #1: MiniG alpha s/q chimera
Macromolecule | Name: MiniG alpha s/q chimera / 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: 47.835914 KDa |
Recombinant expression | Organism: Homo sapiens (human) |
Sequence | String: MVFTLEDFVG DWEQTAAYNL DQVLEQGGVS SLLQNLAVSV TPIQRIVRSG ENALKIDIHV IIPYEGLSAD QMAQIEEVFK VVYPVDDHH FKVILPYGTL VIDGVTPNML NYFGRPYEGI AVFDGKKITV TGTLWNGNKI IDERLITPDG SMLFRVTINS G GGGSGGGG ...String: MVFTLEDFVG DWEQTAAYNL DQVLEQGGVS SLLQNLAVSV TPIQRIVRSG ENALKIDIHV IIPYEGLSAD QMAQIEEVFK VVYPVDDHH FKVILPYGTL VIDGVTPNML NYFGRPYEGI AVFDGKKITV TGTLWNGNKI IDERLITPDG SMLFRVTINS G GGGSGGGG SSGEFEFNSK TEDQRNEEKA QREANKKIEK QLQKDKQVYR ATHRLLLLGA DNSGKSTIVK QMRILHGGSG GS GGTSGIF ETKFQVDKVN FHMFDVGGQR DERRKWIQCF NDVTAIIFVV DSSDYNRLQE ALNLFKSIWN NRWLRTISVI LFL NKQDLL AEKVLAGKSK IEDYFPEFAR YTTPEDATPE PGEDPRVTRA KYFIRDEFLR ISTASGDGRH YCYPHFTCAV DTEN ARRIF NDCKDIILQM NLREYNLV |
-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: 39.418086 KDa |
Recombinant expression | Organism: Homo sapiens (human) |
Sequence | String: MHHHHHHLEV LFQGPGSSGS ELDQLRQEAE QLKNQIRDAR KACADATLSQ ITNNIDPVGR IQMRTRRTLR GHLAKIYAMH WGTDSRLLV SASQDGKLII WDSYTTNKVH AIPLRSSWVM TCAYAPSGNY VACGGLDNIC SIYNLKTREG NVRVSRELAG H TGYLSCCR ...String: MHHHHHHLEV LFQGPGSSGS ELDQLRQEAE QLKNQIRDAR KACADATLSQ ITNNIDPVGR IQMRTRRTLR GHLAKIYAMH WGTDSRLLV SASQDGKLII WDSYTTNKVH AIPLRSSWVM TCAYAPSGNY VACGGLDNIC SIYNLKTREG NVRVSRELAG H TGYLSCCR FLDDNQIVTS SGDTTCALWD IETGQQTTTF TGHTGDVMSL SLAPDTRLFV SGACDASAKL WDVREGMCRQ TF TGHESDI NAICFFPNGN AFATGSDDAT CRLFDLRADQ ELMTYSHDNI ICGITSVSFS KSGRLLLAGY DDFNCNVWDA LKA DRAGVL AGHDNRVSCL GVTDDGMAVA TGSWDSFLKI WN UniProtKB: Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1 |
-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: Homo sapiens (human) |
Sequence | String: MASNNTASIA QARKLVEQLK MEANIDRIKV SKAAADLMAY CEAHAKEDPL LTPVPASENP FREKKFFCAI L UniProtKB: Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2 |
-Macromolecule #4: Nanobody 35
Macromolecule | Name: Nanobody 35 / type: protein_or_peptide / ID: 4 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: Lama glama (llama) |
Molecular weight | Theoretical: 19.726197 KDa |
Recombinant expression | Organism: Lama glama (llama) |
Sequence | String: MKYLLPTAAA GLLLLAAQPA MAQVQLQESG GGLVQPGGSL RLSCAASGFT FSNYKMNWVR QAPGKGLEWV SDISQSGARI SYTGSVKGR FTISRDNAKN TLYLQMNSLK PEDTAVYYCA RCPAPFTRDC FDVTSTTYAY RGQGTQVTVS SLEVLFQGPG H HHHHHHHG SEDQVDPRLI DGK |
-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: Homo sapiens (human) |
Molecular weight | Theoretical: 45.837516 KDa |
Recombinant expression | Organism: Homo sapiens (human) |
Sequence | String: MKTIIALSYI FCLVFADYKD HDGDYKDHDI DYKDDDDKEN LYFQTSFSIL MSPFVPSTIF PVVKWITYVG LGISIGSLIL CLIIEALFW KQIKKSQTSH TRRICMVNIA LSLLIADVWF IVGATVDTTV NPSGVCTAAV FFTHFFYLSL FFWMLMLGIL L AYRIILVF ...String: MKTIIALSYI FCLVFADYKD HDGDYKDHDI DYKDDDDKEN LYFQTSFSIL MSPFVPSTIF PVVKWITYVG LGISIGSLIL CLIIEALFW KQIKKSQTSH TRRICMVNIA LSLLIADVWF IVGATVDTTV NPSGVCTAAV FFTHFFYLSL FFWMLMLGIL L AYRIILVF HHMAQHLMMA VGFCLGYGCP LIISVITIAV TQPSNTYKRK DVCWLNWSNG SKPLLAFVVP ALAIVAVNFV VV LLVLTKL WRPTVGERLS RDDKATIIRV GKSLLILTPL LGLTWGFGIG TIVDSQNLAW HVIFALLNAF QGFFILCFGI LLD SKLRQL LFNKLSALSS WKQTEKQNSS DLSAKPKFSK PFNPLQNKGH YAFSHTGDSS DNIMLTQFVS NEGGGGSGGG GSSG VTGYR LFEEIL UniProtKB: Adhesion G protein-coupled receptor F1 |
-Macromolecule #6: [1-MYRISTOYL-GLYCEROL-3-YL]PHOSPHONYLCHOLINE
Macromolecule | Name: [1-MYRISTOYL-GLYCEROL-3-YL]PHOSPHONYLCHOLINE / type: ligand / ID: 6 / Number of copies: 1 / Formula: LPC |
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Molecular weight | Theoretical: 468.585 Da |
Chemical component information | ChemComp-LPC: |
-Experimental details
-Structure determination
Method | cryo EM |
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Processing | single particle reconstruction |
Aggregation state | particle |
-Sample preparation
Concentration | 8 mg/mL |
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Buffer | pH: 7.5 |
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: 53.5 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: 1.5 µm / Nominal defocus min: 0.5 µm |
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |