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- EMDB-26136: Cryo-EM structure of 7alpha,25-dihydroxycholesterol-bound EBI2/GP... -
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Basic information
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Title | Cryo-EM structure of 7alpha,25-dihydroxycholesterol-bound EBI2/GPR183 in complex with Gi protein | ||||||||||||
![]() | 7alpha,25-dihydroxycholesterol-bound EBI2/GPR183 in complex with Gi protein | ||||||||||||
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Function / homology | ![]() regulation of astrocyte chemotaxis / B cell activation involved in immune response / dendritic cell homeostasis / T follicular helper cell differentiation / mature B cell differentiation involved in immune response / Class A/1 (Rhodopsin-like receptors) / T cell chemotaxis / oxysterol binding / leukocyte chemotaxis / dendritic cell chemotaxis ...regulation of astrocyte chemotaxis / B cell activation involved in immune response / dendritic cell homeostasis / T follicular helper cell differentiation / mature B cell differentiation involved in immune response / Class A/1 (Rhodopsin-like receptors) / T cell chemotaxis / oxysterol binding / leukocyte chemotaxis / dendritic cell chemotaxis / plasma membrane => GO:0005886 / humoral immune response / Adenylate cyclase inhibitory pathway / positive regulation of protein localization to cell cortex / regulation of cAMP-mediated signaling / D2 dopamine receptor binding / G protein-coupled serotonin receptor binding / positive regulation of B cell proliferation / regulation of mitotic spindle organization / cellular response to forskolin / adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway / osteoclast differentiation / Regulation of insulin secretion / G protein-coupled receptor binding / G protein-coupled receptor activity / G-protein beta/gamma-subunit complex binding / Olfactory Signaling Pathway / Activation of the phototransduction cascade / 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 / 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 / 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 / response to peptide hormone / 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 / GDP binding / 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 / phospholipase C-activating G protein-coupled receptor signaling pathway / Ca2+ pathway / cell cortex / midbody / G alpha (i) signalling events / fibroblast proliferation / G alpha (s) signalling events / G alpha (q) signalling events / adaptive immune response / cell population proliferation / Ras protein signal transduction / Extra-nuclear estrogen signaling / positive regulation of ERK1 and ERK2 cascade / immune response / cell cycle / G protein-coupled receptor signaling pathway / cell division / lysosomal membrane / GTPase activity / centrosome / synapse / protein-containing complex binding / nucleolus / GTP binding / magnesium ion binding / signal transduction / extracellular exosome / nucleoplasm / membrane / plasma membrane / cytoplasm Similarity search - Function | ||||||||||||
Biological species | ![]() ![]() ![]() | ||||||||||||
Method | single particle reconstruction / cryo EM / Resolution: 3.12 Å | ||||||||||||
![]() | Chen H / Hung W / Li X | ||||||||||||
Funding support | ![]()
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![]() | ![]() Title: Structures of oxysterol sensor EBI2/GPR183, a key regulator of the immune response. Authors: Hongwen Chen / Weijiao Huang / Xiaochun Li / ![]() Abstract: Oxysterols induce the migration of B-lymphocytes and dendritic cells to interfollicular regions of lymphoid tissues through binding the EBI2 (GPR183) to stimulate effective adaptive immunity and ...Oxysterols induce the migration of B-lymphocytes and dendritic cells to interfollicular regions of lymphoid tissues through binding the EBI2 (GPR183) to stimulate effective adaptive immunity and antibody production during infection. Aberrant EBI2 signaling is implicated in inflammatory bowel disease, sclerosis, and infectious disease. Here, we report the cryo-EM structures of an EBI2-G signaling complex with its endogenous agonist 7α,25-OHC and that of an inactive EBI2 bound to the inverse agonist GSK682753A. These structures reveal an agonist binding site for the oxysterol and a potential ligand entrance site exposed to the lipid bilayer. Mutations within the oxysterol binding site and the Gα interface attenuate G protein signaling and abolish oxysterol-mediated cell migration indicating that G protein signaling directly involves in the oxysterol-EBI2 pathway. Together, these findings provide new insight into how EBI2 is activated by an oxysterol ligand and will facilitate the development of therapeutic approaches that target EBI2-linked diseases. | ||||||||||||
History |
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Structure visualization
Supplemental images |
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Downloads & links
-EMDB archive
Map data | ![]() | 82.7 MB | ![]() | |
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Header (meta data) | ![]() ![]() | 18.5 KB 18.5 KB | Display Display | ![]() |
Images | ![]() | 43.3 KB | ||
Archive directory | ![]() ![]() | HTTPS FTP |
-Validation report
Summary document | ![]() | 400.2 KB | Display | ![]() |
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Full document | ![]() | 399.8 KB | Display | |
Data in XML | ![]() | 6.1 KB | Display | |
Data in CIF | ![]() | 6.9 KB | Display | |
Arichive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 7tuzMC ![]() 7tuyC M: atomic model generated by this map C: citing same article ( |
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Similar structure data | Similarity search - Function & homology ![]() |
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Links
EMDB pages | ![]() ![]() |
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Related items in Molecule of the Month |
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Map
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Annotation | 7alpha,25-dihydroxycholesterol-bound EBI2/GPR183 in complex with Gi protein | ||||||||||||||||||||
Voxel size | X=Y=Z: 0.833 Å | ||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||
Details | EMDB XML:
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-Supplemental data
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Sample components
+Entire : Complex of 7alpha,25-dihydroxycholesterol-bound EBI2/GPR183 with ...
+Supramolecule #1: Complex of 7alpha,25-dihydroxycholesterol-bound EBI2/GPR183 with ...
+Supramolecule #2: G-protein coupled receptor 183
+Supramolecule #3: Guanine nucleotide-binding protein G(i) subunit alpha-1, Guanine ...
+Supramolecule #4: scFv16
+Macromolecule #1: G-protein coupled receptor 183
+Macromolecule #2: Guanine nucleotide-binding protein G(i) subunit alpha-1
+Macromolecule #3: 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 #5: scFv16
+Macromolecule #6: (2S,4aS,4bS,7R,8S,8aS,9R,10aR)-7-[(2R,3R)-7-hydroxy-3,7-dimethylo...
-Experimental details
-Structure determination
Method | cryo EM |
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![]() | single particle reconstruction |
Aggregation state | particle |
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Sample preparation
Buffer | pH: 7.5 |
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Grid | Model: C-flat-1.2/1.3 / Material: GOLD / Mesh: 400 / Support film - Material: CARBON / Support film - topology: HOLEY |
Vitrification | Cryogen name: ETHANE |
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Electron microscopy
Microscope | FEI TITAN |
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Image recording | Film or detector model: GATAN K3 BIOQUANTUM (6k x 4k) / Average electron dose: 60.0 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: ![]() |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: DIFFRACTION / Nominal defocus max: 2.5 µm / Nominal defocus min: 1.2 µm |
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Image processing
Startup model | Type of model: EMDB MAP EMDB ID: |
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Final reconstruction | Resolution.type: BY AUTHOR / Resolution: 3.12 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 496394 |
Initial angle assignment | Type: PROJECTION MATCHING |
Final angle assignment | Type: ANGULAR RECONSTITUTION |