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- EMDB-25176: Cryo-EM structure of human ACKR3 in complex with CXCL12, a small ... -
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Open data
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Basic information
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Title | Cryo-EM structure of human ACKR3 in complex with CXCL12, a small molecule partial agonist CCX662, an extracellular Fab, and an intracellular Fab | ||||||||||||||||||||||||
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Function / homology | ![]() oculomotor nerve development / chemokine (C-X-C motif) ligand 12 signaling pathway / negative regulation of leukocyte tethering or rolling / positive regulation of mesenchymal stem cell migration / C-X-C chemokine binding / response to ultrasound / telencephalon cell migration / regulation of actin polymerization or depolymerization / C-X-C chemokine receptor activity / CXCL12-activated CXCR4 signaling pathway ...oculomotor nerve development / chemokine (C-X-C motif) ligand 12 signaling pathway / negative regulation of leukocyte tethering or rolling / positive regulation of mesenchymal stem cell migration / C-X-C chemokine binding / response to ultrasound / telencephalon cell migration / regulation of actin polymerization or depolymerization / C-X-C chemokine receptor activity / CXCL12-activated CXCR4 signaling pathway / chemokine receptor binding / positive regulation of vasculature development / CXCR chemokine receptor binding / positive regulation of axon extension involved in axon guidance / positive regulation of dopamine secretion / Signaling by ROBO receptors / scavenger receptor activity / induction of positive chemotaxis / integrin activation / C-C chemokine receptor activity / negative regulation of intrinsic apoptotic signaling pathway in response to DNA damage / negative regulation of dendritic cell apoptotic process / cellular response to chemokine / C-C chemokine binding / chemokine-mediated signaling pathway / positive regulation of monocyte chemotaxis / blood circulation / Chemokine receptors bind chemokines / chemokine activity / positive regulation of calcium ion import / detection of temperature stimulus involved in sensory perception of pain / positive regulation of cell adhesion / positive regulation of T cell migration / vasculogenesis / animal organ regeneration / coreceptor activity / detection of mechanical stimulus involved in sensory perception of pain / clathrin-coated pit / Nuclear signaling by ERBB4 / positive regulation of endothelial cell proliferation / positive regulation of neuron differentiation / adult locomotory behavior / cell chemotaxis / calcium-mediated signaling / axon guidance / growth factor activity / neuron migration / response to virus / receptor internalization / recycling endosome / response to peptide hormone / defense response / intracellular calcium ion homeostasis / chemotaxis / integrin binding / G alpha (i) signalling events / positive regulation of cytosolic calcium ion concentration / angiogenesis / collagen-containing extracellular matrix / Estrogen-dependent gene expression / positive regulation of ERK1 and ERK2 cascade / early endosome / cell adhesion / response to hypoxia / endosome / immune response / G protein-coupled receptor signaling pathway / negative regulation of cell population proliferation / external side of plasma membrane / intracellular membrane-bounded organelle / signaling receptor binding / cell surface / signal transduction / extracellular exosome / extracellular region / plasma membrane Similarity search - Function | ||||||||||||||||||||||||
Biological species | ![]() | ||||||||||||||||||||||||
Method | single particle reconstruction / cryo EM / Resolution: 3.3 Å | ||||||||||||||||||||||||
![]() | Yen YC / Schafer CT / Gustavsson M / Handel TM / Tesmer JJG | ||||||||||||||||||||||||
Funding support | ![]()
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![]() | ![]() Title: Structures of atypical chemokine receptor 3 reveal the basis for its promiscuity and signaling bias. Authors: Yu-Chen Yen / Christopher T Schafer / Martin Gustavsson / Stefanie A Eberle / Pawel K Dominik / Dawid Deneka / Penglie Zhang / Thomas J Schall / Anthony A Kossiakoff / John J G Tesmer / Tracy M Handel / ![]() ![]() ![]() Abstract: Both CXC chemokine receptor 4 (CXCR4) and atypical chemokine receptor 3 (ACKR3) are activated by the chemokine CXCL12 yet evoke distinct cellular responses. CXCR4 is a canonical G protein-coupled ...Both CXC chemokine receptor 4 (CXCR4) and atypical chemokine receptor 3 (ACKR3) are activated by the chemokine CXCL12 yet evoke distinct cellular responses. CXCR4 is a canonical G protein-coupled receptor (GPCR), whereas ACKR3 is intrinsically biased for arrestin. The molecular basis for this difference is not understood. Here, we describe cryo-EM structures of ACKR3 in complex with CXCL12, a more potent CXCL12 variant, and a small-molecule agonist. The bound chemokines adopt an unexpected pose relative to those established for CXCR4 and observed in other receptor-chemokine complexes. Along with functional studies, these structures provide insight into the ligand-binding promiscuity of ACKR3, why it fails to couple to G proteins, and its bias toward β-arrestin. The results lay the groundwork for understanding the physiological interplay of ACKR3 with other GPCRs. | ||||||||||||||||||||||||
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Structure visualization
Supplemental images |
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Downloads & links
-EMDB archive
Map data | ![]() | 97.2 MB | ![]() | |
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Header (meta data) | ![]() ![]() | 21.4 KB 21.4 KB | Display Display | ![]() |
FSC (resolution estimation) | ![]() | 10.4 KB | Display | ![]() |
Images | ![]() | 83 KB | ||
Archive directory | ![]() ![]() | HTTPS FTP |
-Validation report
Summary document | ![]() | 425.3 KB | Display | ![]() |
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Full document | ![]() | 424.8 KB | Display | |
Data in XML | ![]() | 11.9 KB | Display | |
Data in CIF | ![]() | 15.6 KB | Display | |
Arichive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 7sk8MC ![]() 7sk3C ![]() 7sk4C ![]() 7sk5C ![]() 7sk6C ![]() 7sk7C ![]() 7sk9C 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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Voxel size | X=Y=Z: 1.08 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 structure of CID25-ACKR3-CXCL12-CCX662-CID24
+Supramolecule #1: Complex structure of CID25-ACKR3-CXCL12-CCX662-CID24
+Macromolecule #1: Atypical chemokine receptor 3
+Macromolecule #2: Stromal cell-derived factor 1
+Macromolecule #3: CID25 Fab light chain
+Macromolecule #4: CID25 Fab heavy chain
+Macromolecule #5: CID24 Fab light chain
+Macromolecule #6: CID24 Fab heavy chain
+Macromolecule #7: CHOLESTEROL
+Macromolecule #8: Lauryl Maltose Neopentyl Glycol
+Macromolecule #9: (1R)-4-[7-(3-carboxypropoxy)-6-methylquinolin-8-yl]-1-{[2-(4-hydr...
-Experimental details
-Structure determination
Method | cryo EM |
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![]() | single particle reconstruction |
Aggregation state | particle |
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Sample preparation
Concentration | 0.2 mg/mL | |||||||||||||||
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Buffer | pH: 8 Component:
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Grid | Model: Quantifoil R1.2/1.3 / Material: COPPER / Mesh: 300 / Support film - Material: CARBON / Support film - topology: HOLEY / Pretreatment - Type: GLOW DISCHARGE / Pretreatment - Atmosphere: AIR | |||||||||||||||
Vitrification | Cryogen name: ETHANE / Chamber humidity: 100 % / Chamber temperature: 277 K / Instrument: FEI VITROBOT MARK IV |
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Electron microscopy
Microscope | FEI TITAN KRIOS |
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Image recording | Film or detector model: GATAN K3 (6k x 4k) / Average electron dose: 53.8 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: ![]() |
Electron optics | C2 aperture diameter: 100.0 µm / Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Cs: 2.7 mm / Nominal defocus max: 3.0 µm / Nominal defocus min: 1.0 µm |
Sample stage | Specimen holder model: FEI TITAN KRIOS AUTOGRID HOLDER / Cooling holder cryogen: NITROGEN |
Experimental equipment | ![]() Model: Titan Krios / Image courtesy: FEI Company |