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Yorodumi- EMDB-21950: Cryo-EM structure of the human chemokine receptor CCR6 in complex... -
+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-21950 | |||||||||
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Title | Cryo-EM structure of the human chemokine receptor CCR6 in complex with CCL20 and a Go protein | |||||||||
Map data | Chemokine receptor CCR6 in complex with CCL20 and a Go protein | |||||||||
Sample |
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Keywords | GPCR / Chemokine / Chemokine receptor / Complex / MEMBRANE PROTEIN | |||||||||
Function / homology | Function and homology information isotype switching to IgA isotypes / DN3 thymocyte differentiation / thymocyte migration / positive regulation of flagellated sperm motility involved in capacitation / CCR6 chemokine receptor binding / sperm principal piece / Beta defensins / regulation of T cell migration / positive regulation of dendritic cell chemotaxis / DN2 thymocyte differentiation ...isotype switching to IgA isotypes / DN3 thymocyte differentiation / thymocyte migration / positive regulation of flagellated sperm motility involved in capacitation / CCR6 chemokine receptor binding / sperm principal piece / Beta defensins / regulation of T cell migration / positive regulation of dendritic cell chemotaxis / DN2 thymocyte differentiation / lymphocyte migration / chemokine receptor activity / CCR chemokine receptor binding / leukocyte migration involved in inflammatory response / C-C chemokine receptor activity / C-C chemokine binding / mu-type opioid receptor binding / corticotropin-releasing hormone receptor 1 binding / G-protein activation / Activation of the phototransduction cascade / Glucagon-type ligand receptors / Thromboxane signalling through TP receptor / Sensory perception of sweet, bitter, and umami (glutamate) taste / G beta:gamma signalling through PI3Kgamma / G beta:gamma signalling through CDC42 / Cooperation of PDCL (PhLP1) and TRiC/CCT in G-protein beta folding / Activation of G protein gated Potassium channels / Inhibition of voltage gated Ca2+ channels via Gbeta/gamma subunits / Ca2+ pathway / G alpha (z) signalling events / Vasopressin regulates renal water homeostasis via Aquaporins / vesicle docking involved in exocytosis / Glucagon-like Peptide-1 (GLP1) regulates insulin secretion / chemokine-mediated signaling pathway / Adrenaline,noradrenaline inhibits insulin secretion / ADP signalling through P2Y purinoceptor 12 / G alpha (q) signalling events / Chemokine receptors bind chemokines / chemokine activity / Thrombin signalling through proteinase activated receptors (PARs) / G alpha (i) signalling events / alkylglycerophosphoethanolamine phosphodiesterase activity / dendritic cell chemotaxis / sperm plasma membrane / photoreceptor outer segment membrane / G protein-coupled dopamine receptor signaling pathway / regulation of heart contraction / spectrin binding / Interleukin-10 signaling / humoral immune response / photoreceptor outer segment / sperm flagellum / T cell migration / positive regulation of T cell migration / cellular defense response / negative regulation of insulin secretion / G protein-coupled serotonin receptor binding / sperm midpiece / cardiac muscle cell apoptotic process / muscle contraction / photoreceptor inner segment / cell chemotaxis / locomotory behavior / calcium-mediated signaling / electron transport chain / G-protein beta/gamma-subunit complex binding / adenylate cyclase-modulating G protein-coupled receptor signaling pathway / G beta:gamma signalling through PLC beta / Presynaptic function of Kainate receptors / Thromboxane signalling through TP receptor / 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 / G beta:gamma signalling through BTK / ADP signalling through P2Y purinoceptor 12 / Glucagon-type ligand receptors / Adrenaline,noradrenaline inhibits insulin secretion / Vasopressin regulates renal water homeostasis via Aquaporins / G alpha (z) signalling events / 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 / G beta:gamma signalling through PI3Kgamma / adenylate cyclase-activating dopamine receptor signaling pathway / Cooperation of PDCL (PhLP1) and TRiC/CCT in G-protein beta folding / chemotaxis / GPER1 signaling / cellular response to prostaglandin E stimulus / G-protein beta-subunit binding / antimicrobial humoral immune response mediated by antimicrobial peptide / heterotrimeric G-protein complex / G alpha (12/13) signalling events / signaling receptor complex adaptor activity / Thrombin signalling through proteinase activated receptors (PARs) / cell-cell signaling Similarity search - Function | |||||||||
Biological species | Rattus norvegicus (Norway rat) / Homo sapiens (human) / Mus musculus (house mouse) | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 3.34 Å | |||||||||
Authors | Wasilko DJ / Johnson ZL | |||||||||
Citation | Journal: Nat Commun / Year: 2020 Title: Structural basis for chemokine receptor CCR6 activation by the endogenous protein ligand CCL20. Authors: David Jonathan Wasilko / Zachary Lee Johnson / Mark Ammirati / Ye Che / Matthew C Griffor / Seungil Han / Huixian Wu / Abstract: Chemokines are important protein-signaling molecules that regulate various immune responses by activating chemokine receptors which belong to the G protein-coupled receptor (GPCR) superfamily. ...Chemokines are important protein-signaling molecules that regulate various immune responses by activating chemokine receptors which belong to the G protein-coupled receptor (GPCR) superfamily. Despite the substantial progression of our structural understanding of GPCR activation by small molecule and peptide agonists, the molecular mechanism of GPCR activation by protein agonists remains unclear. Here, we present a 3.3-Å cryo-electron microscopy structure of the human chemokine receptor CCR6 bound to its endogenous ligand CCL20 and an engineered Go. CCL20 binds in a shallow extracellular pocket, making limited contact with the core 7-transmembrane (TM) bundle. The structure suggests that this mode of binding induces allosterically a rearrangement of a noncanonical toggle switch and the opening of the intracellular crevice for G protein coupling. Our results demonstrate that GPCR activation by a protein agonist does not always require substantial interactions between ligand and the 7TM core region. | |||||||||
History |
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-Structure visualization
Movie |
Movie viewer |
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Structure viewer | EM map: SurfViewMolmilJmol/JSmol |
Supplemental images |
-Downloads & links
-EMDB archive
Map data | emd_21950.map.gz | 201.9 MB | EMDB map data format | |
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Header (meta data) | emd-21950-v30.xml emd-21950.xml | 25.8 KB 25.8 KB | Display Display | EMDB header |
FSC (resolution estimation) | emd_21950_fsc.xml | 13.7 KB | Display | FSC data file |
Images | emd_21950.png | 119.7 KB | ||
Filedesc metadata | emd-21950.cif.gz | 7.7 KB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-21950 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-21950 | HTTPS FTP |
-Validation report
Summary document | emd_21950_validation.pdf.gz | 554.1 KB | Display | EMDB validaton report |
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Full document | emd_21950_full_validation.pdf.gz | 553.7 KB | Display | |
Data in XML | emd_21950_validation.xml.gz | 13.1 KB | Display | |
Data in CIF | emd_21950_validation.cif.gz | 17.7 KB | Display | |
Arichive directory | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-21950 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-21950 | HTTPS FTP |
-Related structure data
Related structure data | 6wwzMC M: atomic model generated by this map C: citing same article (ref.) |
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Similar structure data |
-Links
EMDB pages | EMDB (EBI/PDBe) / EMDataResource |
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Related items in Molecule of the Month |
-Map
File | Download / File: emd_21950.map.gz / Format: CCP4 / Size: 216 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Annotation | Chemokine receptor CCR6 in complex with CCL20 and a Go protein | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Projections & slices | Image control
Images are generated by Spider. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Voxel size | X=Y=Z: 0.87 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Details | EMDB XML:
CCP4 map header:
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-Supplemental data
-Sample components
+Entire : CCR6-CCL20-Go complex
+Supramolecule #1: CCR6-CCL20-Go complex
+Supramolecule #2: Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1,...
+Supramolecule #3: C-C motif chemokine 20, Guanine nucleotide-binding protein G(o) s...
+Supramolecule #4: scFv16
+Macromolecule #1: Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1
+Macromolecule #2: C-C motif chemokine 20
+Macromolecule #3: Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2
+Macromolecule #4: Guanine nucleotide-binding protein G(o) subunit alpha,Guanine nuc...
+Macromolecule #5: scFv16
+Macromolecule #6: C-C chemokine receptor type 6,C-C chemokine receptor type 6
-Experimental details
-Structure determination
Method | cryo EM |
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Processing | single particle reconstruction |
Aggregation state | particle |
-Sample preparation
Concentration | 6.8 mg/mL | |||||||||||||||||||||
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Buffer | pH: 7.5 Component:
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Grid | Model: Quantifoil R1.2/1.3 / Material: GOLD / Mesh: 300 / Support film - Material: CARBON / Support film - topology: HOLEY / Pretreatment - Type: PLASMA CLEANING / Pretreatment - Time: 40 sec. | |||||||||||||||||||||
Vitrification | Cryogen name: ETHANE / Chamber humidity: 100 % / Chamber temperature: 277.0 K / Instrument: FEI VITROBOT MARK IV |
-Electron microscopy
Microscope | FEI TITAN KRIOS |
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Temperature | Min: 80.0 K / Max: 100.0 K |
Specialist optics | Energy filter - Name: GIF Quantum LS / Energy filter - Slit width: 20 eV |
Image recording | Film or detector model: GATAN K2 SUMMIT (4k x 4k) / Detector mode: SUPER-RESOLUTION / Digitization - Dimensions - Width: 3838 pixel / Digitization - Dimensions - Height: 3710 pixel / Digitization - Frames/image: 1-50 / Number grids imaged: 1 / Number real images: 5303 / Average exposure time: 8.0 sec. / Average electron dose: 81.0 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN |
Electron optics | C2 aperture diameter: 100.0 µm / Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Cs: 2.7 mm / Nominal defocus max: 2.0 µm / Nominal defocus min: 0.6 µm / Nominal magnification: 165000 |
Sample stage | Specimen holder model: FEI TITAN KRIOS AUTOGRID HOLDER / Cooling holder cryogen: NITROGEN |
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |
+Image processing
-Atomic model buiding 1
Initial model |
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Refinement | Space: REAL / Protocol: RIGID BODY FIT | ||||||||
Output model | PDB-6wwz: |
-Atomic model buiding 2
Initial model |
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Refinement | Space: REAL / Protocol: FLEXIBLE FIT / Overall B value: 123.52 / Target criteria: Correlation coefficient | ||||||||
Output model | PDB-6wwz: |