+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-35516 | |||||||||
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Title | Cryo-EM structure of the CD97-G13 complex | |||||||||
Map data | ||||||||||
Sample |
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Keywords | adhension GPCR / CD97 / G13 / complex / MEMBRANE PROTEIN | |||||||||
Function / homology | Function and homology information Class B/2 (Secretin family receptors) / secretory granule membrane / 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 / G-protein activation / G protein-coupled acetylcholine receptor signaling pathway ...Class B/2 (Secretin family receptors) / secretory granule membrane / 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 / G-protein activation / G protein-coupled acetylcholine receptor signaling pathway / 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 / adenylate cyclase-activating G protein-coupled receptor signaling pathway / ADP signalling through P2Y purinoceptor 12 / G beta:gamma signalling through BTK / Sensory perception of sweet, bitter, and umami (glutamate) taste / Synthesis, secretion, and inactivation of Glucagon-like Peptide-1 (GLP-1) / 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 / adenylate cyclase-activating dopamine receptor signaling pathway / ADP signalling through P2Y purinoceptor 1 / G beta:gamma signalling through PI3Kgamma / cellular response to prostaglandin E stimulus / Cooperation of PDCL (PhLP1) and TRiC/CCT in G-protein beta folding / sensory perception of taste / GPER1 signaling / G-protein beta-subunit binding / heterotrimeric G-protein complex / Inactivation, recovery and regulation of the phototransduction cascade / extracellular vesicle / G alpha (12/13) signalling events / transmembrane signaling receptor activity / signaling receptor complex adaptor activity / Thrombin signalling through proteinase activated receptors (PARs) / retina development in camera-type eye / cell-cell signaling / GTPase binding / 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 / cell adhesion / immune response / inflammatory response / G protein-coupled receptor signaling pathway / lysosomal membrane / focal adhesion / GTPase activity / synapse / calcium ion binding / Neutrophil degranulation / protein-containing complex binding / signal transduction / extracellular exosome / membrane / plasma membrane / cytosol / cytoplasm Similarity search - Function | |||||||||
Biological species | Homo sapiens (human) | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 2.33 Å | |||||||||
Authors | Mao C / Zhao R / Dong Y / Gao M / Chen L / Zhang C / Xiao P | |||||||||
Funding support | China, 1 items
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Citation | Journal: Mol Cell / Year: 2024 Title: Conformational transitions and activation of the adhesion receptor CD97. Authors: Chunyou Mao / Ru-Jia Zhao / Ying-Jun Dong / Mingxin Gao / Li-Nan Chen / Chao Zhang / Peng Xiao / Jia Guo / Jiao Qin / Dan-Dan Shen / Su-Yu Ji / Shao-Kun Zang / Huibing Zhang / Wei-Wei Wang / ...Authors: Chunyou Mao / Ru-Jia Zhao / Ying-Jun Dong / Mingxin Gao / Li-Nan Chen / Chao Zhang / Peng Xiao / Jia Guo / Jiao Qin / Dan-Dan Shen / Su-Yu Ji / Shao-Kun Zang / Huibing Zhang / Wei-Wei Wang / Qingya Shen / Jin-Peng Sun / Yan Zhang / Abstract: Adhesion G protein-coupled receptors (aGPCRs) are evolutionarily ancient receptors involved in a variety of physiological and pathophysiological processes. Modulators of aGPCR, particularly ...Adhesion G protein-coupled receptors (aGPCRs) are evolutionarily ancient receptors involved in a variety of physiological and pathophysiological processes. Modulators of aGPCR, particularly antagonists, hold therapeutic promise for diseases like cancer and immune and neurological disorders. Hindered by the inactive state structural information, our understanding of antagonist development and aGPCR activation faces challenges. Here, we report the cryo-electron microscopy structures of human CD97, a prototypical aGPCR that plays crucial roles in immune system, in its inactive apo and G13-bound fully active states. Compared with other family GPCRs, CD97 adopts a compact inactive conformation with a constrained ligand pocket. Activation induces significant conformational changes for both extracellular and intracellular sides, creating larger cavities for Stachel sequence binding and G13 engagement. Integrated with functional and metadynamics analyses, our study provides significant mechanistic insights into the activation and signaling of aGPCRs, paving the way for future drug discovery efforts. | |||||||||
History |
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-Structure visualization
Supplemental images |
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-Downloads & links
-EMDB archive
Map data | emd_35516.map.gz | 36.6 MB | EMDB map data format | |
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Header (meta data) | emd-35516-v30.xml emd-35516.xml | 17.9 KB 17.9 KB | Display Display | EMDB header |
Images | emd_35516.png | 33 KB | ||
Filedesc metadata | emd-35516.cif.gz | 6.1 KB | ||
Others | emd_35516_half_map_1.map.gz emd_35516_half_map_2.map.gz | 33.1 MB 33.1 MB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-35516 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-35516 | HTTPS FTP |
-Related structure data
Related structure data | 8iklMC 8ikjC 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_35516.map.gz / Format: CCP4 / Size: 42.9 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||
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Voxel size | X=Y=Z: 0.93 Å | ||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||
Details | EMDB XML:
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-Supplemental data
-Half map: #2
File | emd_35516_half_map_1.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Half map: #1
File | emd_35516_half_map_2.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Sample components
-Entire : Adhesion G protein-coupled receptor E5
Entire | Name: Adhesion G protein-coupled receptor E5 |
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Components |
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-Supramolecule #1: Adhesion G protein-coupled receptor E5
Supramolecule | Name: Adhesion G protein-coupled receptor E5 / type: organelle_or_cellular_component / ID: 1 / Parent: 0 / Macromolecule list: all |
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Source (natural) | Organism: Homo sapiens (human) |
-Macromolecule #1: Adhesion G protein-coupled receptor E5
Macromolecule | Name: Adhesion G protein-coupled receptor E5 / 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: 31.429586 KDa |
Recombinant expression | Organism: Fusarium sinicum (fungus) |
Sequence | String: SSFAILMAHY DVEDWKLTLI TRVGLALSLF CLLLCILTFL LVRPIQGSRT TIHLHLCICL FVGSTIFLAG IENEGGQVGL RCRLVAGLL HYCFLAAFCW MSLEGLELYF LVVRVFQGQG LSTRWLCLIG YGVPLLIVGV SAAIYSKGYG RPRYCWLDFE Q GFLWSFLG ...String: SSFAILMAHY DVEDWKLTLI TRVGLALSLF CLLLCILTFL LVRPIQGSRT TIHLHLCICL FVGSTIFLAG IENEGGQVGL RCRLVAGLL HYCFLAAFCW MSLEGLELYF LVVRVFQGQG LSTRWLCLIG YGVPLLIVGV SAAIYSKGYG RPRYCWLDFE Q GFLWSFLG PVTFIILCNA VIFVTTVWKL TQKFSEINPD MKKLKKARAL TITAIAQLFL LGCTWVFGLF IFDDRSLVLT YV FTILNCL QGAFLYLLHC LLNKKVREEY RKWACLVAGG S UniProtKB: Adhesion G protein-coupled receptor E5 |
-Macromolecule #2: Guanine nucleotide-binding protein G(13) subunit alpha isoforms short
Macromolecule | Name: Guanine nucleotide-binding protein G(13) subunit alpha isoforms short 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: 26.503432 KDa |
Recombinant expression | Organism: Fusarium sinicum (fungus) |
Sequence | String: GCTLSAEDKA AVERSKMIDK CLSREKTYVK RLVKILLLGA DNSGKSTFLK QMRIIHGGSG GSGGTKGIHE YDFEIKNVPF KMVDVGGQR SERKRWFECF DSVTSILFLV DSSDFNRLTE SLNDFETIVN NRVFSNVSII LFLNKTDLLE EKVQIVSIKD Y FLEFEGDP ...String: GCTLSAEDKA AVERSKMIDK CLSREKTYVK RLVKILLLGA DNSGKSTFLK QMRIIHGGSG GSGGTKGIHE YDFEIKNVPF KMVDVGGQR SERKRWFECF DSVTSILFLV DSSDFNRLTE SLNDFETIVN NRVFSNVSII LFLNKTDLLE EKVQIVSIKD Y FLEFEGDP HCLRDVQKFL VECFRNKRRD QQQKPLYHHF TTAINTENAR LIFRDVKDTI LHDNLKQLML Q |
-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: Homo sapiens (human) |
Molecular weight | Theoretical: 37.198656 KDa |
Recombinant expression | Organism: Spodoptera frugiperda (fall armyworm) |
Sequence | String: ELDQLRQEAE QLKNQIRDAR KACADATLSQ ITNNIDPVGR IQMRTRRTLR GHLAKIYAMH WGTDSRLLVS ASQDGKLIIW DSYTTNKVH AIPLRSSWVM TCAYAPSGNY VACGGLDNIC SIYNLKTREG NVRVSRELAG HTGYLSCCRF LDDNQIVTSS G DTTCALWD ...String: ELDQLRQEAE QLKNQIRDAR KACADATLSQ ITNNIDPVGR IQMRTRRTLR GHLAKIYAMH WGTDSRLLVS ASQDGKLIIW DSYTTNKVH AIPLRSSWVM TCAYAPSGNY VACGGLDNIC SIYNLKTREG NVRVSRELAG HTGYLSCCRF LDDNQIVTSS G DTTCALWD IETGQQTTTF TGHTGDVMSL SLAPDTRLFV SGACDASAKL WDVREGMCRQ TFTGHESDIN AICFFPNGNA FA TGSDDAT CRLFDLRADQ ELMTYSHDNI ICGITSVSFS KSGRLLLAGY DDFNCNVWDA LKADRAGVLA GHDNRVSCLG VTD DGMAVA TGSWDSFLKI WN 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: Homo sapiens (human) |
Molecular weight | Theoretical: 7.861143 KDa |
Recombinant expression | Organism: Spodoptera frugiperda (fall armyworm) |
Sequence | String: MASNNTASIA QARKLVEQLK MEANIDRIKV SKAAADLMAY CEAHAKEDPL LTPVPASENP FREKKFFCAI L UniProtKB: Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2 |
-Experimental details
-Structure determination
Method | cryo EM |
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Processing | single particle reconstruction |
Aggregation state | particle |
-Sample preparation
Buffer | pH: 7.5 |
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Grid | Model: Quantifoil R1.2/1.3 / Material: GOLD / Mesh: 300 |
Vitrification | Cryogen name: ETHANE |
-Electron microscopy
Microscope | FEI TITAN KRIOS |
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Electron beam | Acceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELDBright-field microscopy / Cs: 2.7 mm / Nominal defocus max: 1.5 µm / Nominal defocus min: 0.7000000000000001 µm |
Sample stage | Specimen holder model: FEI TITAN KRIOS AUTOGRID HOLDER / Cooling holder cryogen: NITROGEN |
Image recording | Film or detector model: FEI FALCON IV (4k x 4k) / Average electron dose: 52.0 e/Å2 |
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |
-Image processing
Startup model | Type of model: NONE |
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Initial angle assignment | Type: RANDOM ASSIGNMENT |
Final angle assignment | Type: MAXIMUM LIKELIHOOD |
Final reconstruction | Resolution.type: BY AUTHOR / Resolution: 2.33 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 252319 |