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- PDB-7sk3: Cryo-EM structure of ACKR3 in complex with CXCL12, an intracellul... -
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Open data
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Basic information
Entry | Database: PDB / ID: 7sk3 | ||||||||||||||||||||||||
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Title | Cryo-EM structure of ACKR3 in complex with CXCL12, an intracellular Fab, and an extracellular Fab | ||||||||||||||||||||||||
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![]() | SIGNALING PROTEIN/IMMUNE SYSTEM / Atypical Chemokine Receptor / MEMBRANE PROTEIN / SIGNALING PROTEIN / SIGNALING PROTEIN-IMMUNE SYSTEM complex | ||||||||||||||||||||||||
Function / homology | ![]() oculomotor nerve development / chemokine (C-X-C motif) ligand 12 signaling pathway / negative regulation of leukocyte tethering or rolling / C-X-C chemokine binding / positive regulation of mesenchymal stem cell migration / 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 / C-X-C chemokine binding / positive regulation of mesenchymal stem cell migration / 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 / C-C chemokine receptor activity / Signaling by ROBO receptors / scavenger receptor activity / C-C chemokine binding / induction of positive chemotaxis / integrin activation / negative regulation of intrinsic apoptotic signaling pathway in response to DNA damage / negative regulation of dendritic cell apoptotic process / cellular response to chemokine / positive regulation of monocyte chemotaxis / chemokine-mediated signaling pathway / 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 / cell chemotaxis / adult locomotory behavior / axon guidance / calcium-mediated signaling / growth factor activity / neuron migration / response to virus / recycling endosome / receptor internalization / response to peptide hormone / defense response / intracellular calcium ion homeostasis / chemotaxis / integrin binding / positive regulation of cytosolic calcium ion concentration / G alpha (i) signalling events / angiogenesis / collagen-containing extracellular matrix / Estrogen-dependent gene expression / positive regulation of ERK1 and ERK2 cascade / early endosome / response to hypoxia / cell adhesion / 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 | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.8 Å | ||||||||||||||||||||||||
![]() | Yen, Y.C. / Schafer, C.T. / Gustavsson, M. / Handel, T.M. / Tesmer, J.J.G. | ||||||||||||||||||||||||
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. | ||||||||||||||||||||||||
History |
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Structure visualization
Structure viewer | Molecule: ![]() ![]() |
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Downloads & links
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Download
PDBx/mmCIF format | ![]() | 296.3 KB | Display | ![]() |
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PDB format | ![]() | 243.9 KB | Display | ![]() |
PDBx/mmJSON format | ![]() | Tree view | ![]() | |
Others | ![]() |
-Validation report
Arichive directory | ![]() ![]() | HTTPS FTP |
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-Related structure data
Related structure data | ![]() 25171MC ![]() 7sk4C ![]() 7sk5C ![]() 7sk6C ![]() 7sk7C ![]() 7sk8C ![]() 7sk9C 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
-Protein , 2 types, 2 molecules AB
#1: Protein | Mass: 45196.406 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() |
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#2: Protein | Mass: 7978.460 Da / Num. of mol.: 1 / Fragment: UNP residues 22-89 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() Production host: ![]() ![]() References: UniProt: P48061 |
-Antibody , 4 types, 4 molecules CDEF
#3: Antibody | Mass: 23531.129 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() Production host: ![]() ![]() |
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#4: Antibody | Mass: 25461.383 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() Production host: ![]() ![]() |
#5: Antibody | Mass: 23471.031 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() Production host: ![]() ![]() |
#6: Antibody | Mass: 25380.223 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() Production host: ![]() ![]() |
-Non-polymers , 1 types, 8 molecules ![](data/chem/img/CLR.gif)
#7: Chemical | ChemComp-CLR / |
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-Details
Has ligand of interest | Y |
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-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
Component | Name: Complex structure of CID25-ACKR3-CXCL12- CID24 / Type: COMPLEX / Entity ID: #1-#6 / Source: MULTIPLE SOURCES | |||||||||||||||||||||||||
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Molecular weight | Experimental value: NO | |||||||||||||||||||||||||
Buffer solution | pH: 8 | |||||||||||||||||||||||||
Buffer component |
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Specimen | Conc.: 0.2 mg/ml / Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES | |||||||||||||||||||||||||
Specimen support | Grid material: COPPER / Grid mesh size: 300 divisions/in. / Grid type: Quantifoil R1.2/1.3 | |||||||||||||||||||||||||
Vitrification | Instrument: FEI VITROBOT MARK IV / Cryogen name: ETHANE / Humidity: 100 % / Chamber temperature: 277 K |
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Electron microscopy imaging
Experimental equipment | ![]() Model: Titan Krios / Image courtesy: FEI Company |
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Microscopy | Model: FEI TITAN KRIOS |
Electron gun | Electron source: ![]() |
Electron lens | Mode: BRIGHT FIELD / Nominal defocus max: 3000 nm / Nominal defocus min: 1000 nm / Cs: 2.7 mm / C2 aperture diameter: 100 µm |
Specimen holder | Cryogen: NITROGEN / Specimen holder model: FEI TITAN KRIOS AUTOGRID HOLDER |
Image recording | Electron dose: 53.8 e/Å2 / Film or detector model: GATAN K3 (6k x 4k) |
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Processing
Software | Name: PHENIX / Version: 1.20_4459: / Classification: refinement | ||||||||||||||||||||||||
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EM software |
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CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION | ||||||||||||||||||||||||
Symmetry | Point symmetry: C1 (asymmetric) | ||||||||||||||||||||||||
3D reconstruction | Resolution: 3.8 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 528797 / Symmetry type: POINT | ||||||||||||||||||||||||
Refine LS restraints |
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