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Yorodumi- PDB-7sk9: Cryo-EM structure of human ACKR3 in complex with a small molecule... -
+Open data
-Basic information
Entry | Database: PDB / ID: 7sk9 | ||||||||||||||||||||||||
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Title | Cryo-EM structure of human ACKR3 in complex with a small molecule partial agonist CCX662, and an intracellular Fab | ||||||||||||||||||||||||
Components |
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Keywords | SIGNALING PROTEIN/IMMUNE SYSTEM / Atypical Chemokine Receptor / MEMBRANE PROTEIN / SIGNALING PROTEIN / SIGNALING PROTEIN-IMMUNE SYSTEM complex | ||||||||||||||||||||||||
Function / homology | Function and homology information oculomotor nerve development / C-X-C chemokine binding / positive regulation of mesenchymal stem cell migration / C-X-C chemokine receptor activity / C-C chemokine receptor activity / scavenger receptor activity / C-C chemokine binding / negative regulation of intrinsic apoptotic signaling pathway in response to DNA damage / chemokine-mediated signaling pathway / Chemokine receptors bind chemokines ...oculomotor nerve development / C-X-C chemokine binding / positive regulation of mesenchymal stem cell migration / C-X-C chemokine receptor activity / C-C chemokine receptor activity / scavenger receptor activity / C-C chemokine binding / negative regulation of intrinsic apoptotic signaling pathway in response to DNA damage / chemokine-mediated signaling pathway / Chemokine receptors bind chemokines / vasculogenesis / coreceptor activity / clathrin-coated pit / cell chemotaxis / calcium-mediated signaling / recycling endosome / receptor internalization / positive regulation of cytosolic calcium ion concentration / G alpha (i) signalling events / angiogenesis / positive regulation of ERK1 and ERK2 cascade / early endosome / cell adhesion / endosome / immune response / negative regulation of cell population proliferation / external side of plasma membrane / intracellular membrane-bounded organelle / cell surface / plasma membrane Similarity search - Function | ||||||||||||||||||||||||
Biological species | Homo sapiens (human) | ||||||||||||||||||||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.7 Å | ||||||||||||||||||||||||
Authors | Yen, Y.C. / Schafer, C.T. / Gustavsson, M. / Handel, T.M. / Tesmer, J.J.G. | ||||||||||||||||||||||||
Funding support | United States, 7items
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Citation | Journal: Sci Adv / Year: 2022 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: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 7sk9.cif.gz | 245.2 KB | Display | PDBx/mmCIF format |
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PDB format | pdb7sk9.ent.gz | 201.9 KB | Display | PDB format |
PDBx/mmJSON format | 7sk9.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/sk/7sk9 ftp://data.pdbj.org/pub/pdb/validation_reports/sk/7sk9 | HTTPS FTP |
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-Related structure data
Related structure data | 25177MC 7sk3C 7sk4C 7sk5C 7sk6C 7sk7C 7sk8C M: map data used to model this data C: citing same article (ref.) |
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Similar structure data | Similarity search - Function & homologyF&H Search |
-Links
-Assembly
Deposited unit |
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1 |
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-Components
#1: Protein | Mass: 45196.406 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: ACKR3, CMKOR1, CXCR7, GPR159, RDC1 / Production host: Spodoptera frugiperda (fall armyworm) / References: UniProt: P25106 | ||
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#2: Antibody | Mass: 25380.223 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) Production host: Escherichia coli 'BL21-Gold(DE3)pLysS AG' (bacteria) | ||
#3: Antibody | Mass: 23471.031 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) Production host: Escherichia coli 'BL21-Gold(DE3)pLysS AG' (bacteria) | ||
#4: Chemical | ChemComp-GJ9 / ( | ||
#5: Chemical | 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 |
-Sample preparation
Component | Name: Complex structure of ACKR3-CCX662- CID24 / Type: COMPLEX / Entity ID: #1-#3 / 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 |
-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: FIELD EMISSION GUN / Accelerating voltage: 300 kV / Illumination mode: FLOOD BEAM |
Electron lens | Mode: BRIGHT FIELD / 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) |
-Processing
Software | Name: PHENIX / Version: 1.19.2_4158: / 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: 3.7 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 297347 / Symmetry type: POINT | ||||||||||||||||||||||||
Refine LS restraints |
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