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Open data
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Basic information
Entry | Database: PDB / ID: 7tuy | ||||||||||||
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Title | Cryo-EM structure of GSK682753A-bound EBI2/GPR183 | ||||||||||||
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![]() | IMMUNE SYSTEM / EBI2 / GPR183 / oxysterol / GPCR / signaling / immunity / immunocyte migration | ||||||||||||
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 / positive regulation of B cell proliferation / osteoclast differentiation / G protein-coupled receptor activity / G alpha (i) signalling events / adaptive immune response / positive regulation of ERK1 and ERK2 cascade / immune response / G protein-coupled receptor signaling pathway / plasma membrane Similarity search - Function | ||||||||||||
Biological species | ![]() synthetic construct (others) ![]() ![]() | ||||||||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 2.98 Å | ||||||||||||
![]() | Chen, H. / Huang, 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
Structure viewer | Molecule: ![]() ![]() |
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Downloads & links
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Download
PDBx/mmCIF format | ![]() | 172.2 KB | Display | ![]() |
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PDB format | ![]() | 134.5 KB | Display | ![]() |
PDBx/mmJSON format | ![]() | Tree view | ![]() | |
Others | ![]() |
-Validation report
Arichive directory | ![]() ![]() | HTTPS FTP |
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-Related structure data
Related structure data | ![]() 26135MC ![]() 7tuzC M: map data used to model this data C: citing same article ( |
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Similar structure data | Similarity search - Function & homology ![]() |
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Links
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Assembly
Deposited unit | ![]()
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Components
#1: Antibody | Mass: 24321.084 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() Production host: ![]() ![]() |
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#2: Antibody | Mass: 15071.431 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) synthetic construct (others) Production host: ![]() ![]() |
#3: Antibody | Mass: 23483.062 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() Production host: ![]() ![]() |
#4: Protein | Mass: 54364.539 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() Gene: GPR183, EBI2 / Cell line (production host): HEK203S GnTI- / Production host: ![]() |
#5: Chemical | ChemComp-KKF / |
Has ligand of interest | Y |
-Experimental details
-Experiment
Experiment | Method: ELECTRON MICROSCOPY |
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EM experiment | Aggregation state: PARTICLE / 3D reconstruction method: single particle reconstruction |
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Sample preparation
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Molecular weight | Experimental value: NO | ||||||||||||||||||||||||||||||
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Buffer solution | pH: 7.5 | ||||||||||||||||||||||||||||||
Specimen | Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES | ||||||||||||||||||||||||||||||
Specimen support | Grid material: GOLD / Grid mesh size: 400 divisions/in. / Grid type: C-flat-1.2/1.3 | ||||||||||||||||||||||||||||||
Vitrification | Cryogen name: ETHANE / Humidity: 100 % / Chamber temperature: 293 K |
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Electron microscopy imaging
Microscopy | Model: FEI TITAN |
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Electron gun | Electron source: ![]() |
Electron lens | Mode: DIFFRACTION / Nominal defocus max: 2500 nm / Nominal defocus min: 1200 nm |
Image recording | Electron dose: 60 e/Å2 / Film or detector model: GATAN K3 BIOQUANTUM (6k x 4k) |
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Processing
Software | Name: PHENIX / Version: 1.16_3549: / Classification: refinement | ||||||||||||||||||||||||
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EM software | Name: SerialEM / Category: image acquisition | ||||||||||||||||||||||||
CTF correction | Type: NONE | ||||||||||||||||||||||||
3D reconstruction | Resolution: 2.98 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 222283 / Symmetry type: POINT | ||||||||||||||||||||||||
Refine LS restraints |
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