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Yorodumi- EMDB-31232: Structural basis for the tethered peptide activation of adhesion GPCRs -
+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-31232 | |||||||||
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Title | Structural basis for the tethered peptide activation of adhesion GPCRs | |||||||||
Map data | ||||||||||
Sample |
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Function / homology | Function and homology information plasma membrane => GO:0005886 / 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 ...plasma membrane => GO:0005886 / 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 / 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 / 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 / Extra-nuclear estrogen signaling / cell population proliferation / membrane => GO:0016020 / cell surface receptor signaling pathway / G protein-coupled receptor signaling pathway / lysosomal membrane / GTPase activity / synapse / protein-containing complex binding / signal transduction / extracellular exosome / nucleoplasm / membrane / plasma membrane / cytoplasm / cytosol Similarity search - Function | |||||||||
Biological species | Homo sapiens (human) | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 3.1 Å | |||||||||
Authors | Ping Y-Q / Xiao P / Yang F / Zhao R-J / Guo S-C / Yan X / Wu X / Sun J-P | |||||||||
Funding support | China, 1 items
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Citation | Journal: Nature / Year: 2022 Title: Structural basis for the tethered peptide activation of adhesion GPCRs. Authors: Yu-Qi Ping / Peng Xiao / Fan Yang / Ru-Jia Zhao / Sheng-Chao Guo / Xu Yan / Xiang Wu / Chao Zhang / Yan Lu / Fenghui Zhao / Fulai Zhou / Yue-Tong Xi / Wanchao Yin / Feng-Zhen Liu / Dong-Fang ...Authors: Yu-Qi Ping / Peng Xiao / Fan Yang / Ru-Jia Zhao / Sheng-Chao Guo / Xu Yan / Xiang Wu / Chao Zhang / Yan Lu / Fenghui Zhao / Fulai Zhou / Yue-Tong Xi / Wanchao Yin / Feng-Zhen Liu / Dong-Fang He / Dao-Lai Zhang / Zhong-Liang Zhu / Yi Jiang / Lutao Du / Shi-Qing Feng / Torsten Schöneberg / Ines Liebscher / H Eric Xu / Jin-Peng Sun / Abstract: Adhesion G-protein-coupled receptors (aGPCRs) are important for organogenesis, neurodevelopment, reproduction and other processes. Many aGPCRs are activated by a conserved internal (tethered) agonist ...Adhesion G-protein-coupled receptors (aGPCRs) are important for organogenesis, neurodevelopment, reproduction and other processes. Many aGPCRs are activated by a conserved internal (tethered) agonist sequence known as the Stachel sequence. Here, we report the cryogenic electron microscopy (cryo-EM) structures of two aGPCRs in complex with G: GPR133 and GPR114. The structures indicate that the Stachel sequences of both receptors assume an α-helical-bulge-β-sheet structure and insert into a binding site formed by the transmembrane domain (TMD). A hydrophobic interaction motif (HIM) within the Stachel sequence mediates most of the intramolecular interactions with the TMD. Combined with the cryo-EM structures, biochemical characterization of the HIM motif provides insight into the cross-reactivity and selectivity of the Stachel sequences. Two interconnected mechanisms, the sensing of Stachel sequences by the conserved 'toggle switch' W and the constitution of a hydrogen-bond network formed by Q/Y and the P/VφφG motif (φ indicates a hydrophobic residue), are important in Stachel sequence-mediated receptor activation and G coupling. Notably, this network stabilizes kink formation in TM helices 6 and 7 (TM6 and TM7, respectively). A common G-binding interface is observed between the two aGPCRs, and GPR114 has an extended TM7 that forms unique interactions with G. Our structures reveal the detailed mechanisms of aGPCR activation by Stachel sequences and their G coupling. | |||||||||
History |
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-Structure visualization
Supplemental images |
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-Downloads & links
-EMDB archive
Map data | emd_31232.map.gz | 26.4 MB | EMDB map data format | |
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Header (meta data) | emd-31232-v30.xml emd-31232.xml | 10.5 KB 10.5 KB | Display Display | EMDB header |
Images | emd_31232.png | 34.6 KB | ||
Masks | emd_31232_msk_1.map | 30.5 MB | Mask map | |
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-31232 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-31232 | HTTPS FTP |
-Validation report
Summary document | emd_31232_validation.pdf.gz | 350.5 KB | Display | EMDB validaton report |
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Full document | emd_31232_full_validation.pdf.gz | 350 KB | Display | |
Data in XML | emd_31232_validation.xml.gz | 5.7 KB | Display | |
Data in CIF | emd_31232_validation.cif.gz | 6.5 KB | Display | |
Arichive directory | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-31232 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-31232 | HTTPS FTP |
-Related structure data
Related structure data | 7eptMC 7eq1C 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_31232.map.gz / Format: CCP4 / Size: 30.5 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||
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Voxel size | X=Y=Z: 1.071 Å | ||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||
Details | EMDB XML:
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-Supplemental data
-Mask #1
File | emd_31232_msk_1.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Sample components
-Entire : GPR133-Gs complex
Entire | Name: GPR133-Gs complex |
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Components |
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-Supramolecule #1: GPR133-Gs complex
Supramolecule | Name: GPR133-Gs complex / type: complex / Chimera: Yes / ID: 1 / Parent: 0 / Macromolecule list: all |
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Source (natural) | Organism: Homo sapiens (human) |
Recombinant expression | Organism: Spodoptera frugiperda (fall armyworm) |
-Macromolecule #1: GPR133
Macromolecule | Name: GPR133 / type: protein_or_peptide / ID: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: Homo sapiens (human) |
Sequence | String: TNFAILMQVV PLELARGHQV ALSSISYVGC SLSVLCLVAT LVTFAVLSSV STIRNQRYHI HANLSFAVLV AQVLLLIS F RLEPGTTPCQ VMAVLLHYFF LSAFAWMLVE GLHLYSMVIK VFGSEDSKHR YYYGMGWGFP LLICIISLSF AMDSYGTSN NCWLSLASGA ...String: TNFAILMQVV PLELARGHQV ALSSISYVGC SLSVLCLVAT LVTFAVLSSV STIRNQRYHI HANLSFAVLV AQVLLLIS F RLEPGTTPCQ VMAVLLHYFF LSAFAWMLVE GLHLYSMVIK VFGSEDSKHR YYYGMGWGFP LLICIISLSF AMDSYGTSN NCWLSLASGA IWAFVAPALF VIVVNIGILI AVTRVISQIS ADNYKIHGDP SAFKLTAKAV AVLLPILGTS WVFGVLAVNG CAVVFQYMF ATLNSLQGLF IFLFHCLLNS EVRAAFKHKT KVWSLT |
-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: 7.4 |
Grid | Material: GOLD / Mesh: 300 |
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: 70.0 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Cs: 2.7 mm / Nominal defocus max: 2.2 µm / Nominal defocus min: 1.2 µm |
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |
-Image processing
Final reconstruction | Resolution.type: BY AUTHOR / Resolution: 3.1 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 575193 |
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Initial angle assignment | Type: ANGULAR RECONSTITUTION |
Final angle assignment | Type: OTHER |