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- EMDB-25173: Cryo-EM structure of ACKR3 in complex with CXCL12 and an intracel... -
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Open data
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Basic information
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Title | Cryo-EM structure of ACKR3 in complex with CXCL12 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 / response to ultrasound / C-X-C chemokine binding / 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 / response to ultrasound / C-X-C chemokine binding / telencephalon cell migration / regulation of actin polymerization or depolymerization / C-X-C chemokine receptor activity / CXCL12-activated CXCR4 signaling pathway / ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() Similarity search - Function | ||||||||||||||||||||||||
Biological species | ![]() ![]() ![]() ![]() ![]() | ||||||||||||||||||||||||
Method | ![]() ![]() | ||||||||||||||||||||||||
![]() | 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. | ||||||||||||||||||||||||
History |
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Structure visualization
Supplemental images |
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Downloads & links
-EMDB archive
Map data | ![]() | 97.1 MB | ![]() | |
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Header (meta data) | ![]() ![]() | 19.1 KB 19.1 KB | Display Display | ![]() |
FSC (resolution estimation) | ![]() | 10.4 KB | Display | ![]() |
Images | ![]() | 85.2 KB | ||
Archive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 7sk5MC ![]() 7sk3C ![]() 7sk4C ![]() 7sk6C ![]() 7sk7C ![]() 7sk8C ![]() 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 ACKR3-CXCL12-CID24-NB
Entire | Name: Complex structure of ACKR3-CXCL12-CID24-NB |
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Components |
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-Supramolecule #1: Complex structure of ACKR3-CXCL12-CID24-NB
Supramolecule | Name: Complex structure of ACKR3-CXCL12-CID24-NB / type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1-#5 |
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-Macromolecule #1: Atypical chemokine receptor 3
Macromolecule | Name: Atypical chemokine receptor 3 / type: protein_or_peptide / ID: 1 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() ![]() |
Molecular weight | Theoretical: 45.196406 KDa |
Recombinant expression | Organism: ![]() ![]() ![]() |
Sequence | String: GAPDLHLFDY SEPGNFSDIS WPCNSSDCIV VDTVMCPNMP NKSVLLYTLS FIYIFIFVIG MIANSVVVWV NIQAKTTGYD THCYILNLA IADLWVVLTI PVWVVSLVQH NQWPMGELTC KVTHLIFSIN LFGSIFFLTC MSVDRYLSIT YFTNTPSSRK K MVRRVVCI ...String: GAPDLHLFDY SEPGNFSDIS WPCNSSDCIV VDTVMCPNMP NKSVLLYTLS FIYIFIFVIG MIANSVVVWV NIQAKTTGYD THCYILNLA IADLWVVLTI PVWVVSLVQH NQWPMGELTC KVTHLIFSIN LFGSIFFLTC MSVDRYLSIT YFTNTPSSRK K MVRRVVCI LVWLLAFCVS LPDTYYLKTV TSASNNETYC RSFYPEHSIK EWLIGMELVS VVLGFAVPFS IIAVFYFLLA RA ISASSDQ EKHSSRKIIF SYVVVFLVCW LPYHVAVLLD IFSILHYIPF TCRLEHALFT ALHVTQCLSL VHCCVNPVLY SFI NRNYRY ELMKAFIFKY SAKTGLTKLI DASRVSETEY SALEQSTKGR PLEVLFQGPH HHHHHHHHHD YKDDDDK |
-Macromolecule #2: CID24 Fab heavy chain
Macromolecule | Name: CID24 Fab heavy chain / type: protein_or_peptide / ID: 2 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() ![]() |
Molecular weight | Theoretical: 25.380223 KDa |
Recombinant expression | Organism: ![]() ![]() ![]() |
Sequence | String: EISEVQLVES GGGLVQPGGS LRLSCAASGF NISSSSIHWV RQAPGKGLEW VASISPSYGY TSYADSVKGR FTISADTSKN TAYLQMNSL RAEDTAVYYC ARVSYWDWTW GWSKYEGMDY WGQGTLVTVS SASTKGPSVF PLAPSSKSTS GGTAALGCLV K DYFPEPVT ...String: EISEVQLVES GGGLVQPGGS LRLSCAASGF NISSSSIHWV RQAPGKGLEW VASISPSYGY TSYADSVKGR FTISADTSKN TAYLQMNSL RAEDTAVYYC ARVSYWDWTW GWSKYEGMDY WGQGTLVTVS SASTKGPSVF PLAPSSKSTS GGTAALGCLV K DYFPEPVT VSWNSGALTS GVHTFPAVLQ SSGLYSLSSV VTVPSSSLGT QTYICNVNHK PSNTKVDKKV EPKSCDKTHT |
-Macromolecule #3: Stromal cell-derived factor 1
Macromolecule | Name: Stromal cell-derived factor 1 / type: protein_or_peptide / ID: 3 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() ![]() |
Molecular weight | Theoretical: 7.97846 KDa |
Recombinant expression | Organism: ![]() ![]() ![]() |
Sequence | String: KPVSLSYRCP CRFFESHVAR ANVKHLKILN TPNCALQIVA RLKNNNRQVC IDPKLKWIQE YLEKALNK |
-Macromolecule #4: CID24 Fab light chain
Macromolecule | Name: CID24 Fab light chain / type: protein_or_peptide / ID: 4 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() ![]() |
Molecular weight | Theoretical: 23.471031 KDa |
Recombinant expression | Organism: ![]() ![]() ![]() |
Sequence | String: SDIQMTQSPS SLSASVGDRV TITCRASQSV SSAVAWYQQK PGKAPKLLIY SASSLYSGVP SRFSGSRSGT DFTLTISSLQ PEDFATYYC QQSYYYPITF GQGTKVEIKR TVAAPSVFIF PPSDSQLKSG TASVVCLLNN FYPREAKVQW KVDNALQSGN S QESVTEQD ...String: SDIQMTQSPS SLSASVGDRV TITCRASQSV SSAVAWYQQK PGKAPKLLIY SASSLYSGVP SRFSGSRSGT DFTLTISSLQ PEDFATYYC QQSYYYPITF GQGTKVEIKR TVAAPSVFIF PPSDSQLKSG TASVVCLLNN FYPREAKVQW KVDNALQSGN S QESVTEQD SKDSTYSLSS TLTLSKADYE KHKVYACEVT HQGLSSPVTK SFNRGEC |
-Macromolecule #5: Anti-Fab nanobody
Macromolecule | Name: Anti-Fab nanobody / type: protein_or_peptide / ID: 5 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() ![]() ![]() |
Molecular weight | Theoretical: 13.390644 KDa |
Recombinant expression | Organism: ![]() ![]() ![]() |
Sequence | String: GSQVQLQESG GGLVQPGGSL RLSCAASGRT ISRYAMSWFR QAPGKEREFV AVARRSGDGA FYADSVQGRF TVSRDDAKNT VYLQMNSLK PEDTAVYYCA IDSDTFYSGS YDYWGQGTQV TVSS |
-Macromolecule #6: CHOLESTEROL
Macromolecule | Name: CHOLESTEROL / type: ligand / ID: 6 / Number of copies: 7 / Formula: CLR |
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Molecular weight | Theoretical: 386.654 Da |
Chemical component information | ![]() ChemComp-CLR: |
-Experimental details
-Structure determination
Method | ![]() |
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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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Electron beam | Acceleration voltage: 300 kV / Electron source: ![]() |
Electron optics | C2 aperture diameter: 100.0 µm / Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD![]() |
Sample stage | Specimen holder model: FEI TITAN KRIOS AUTOGRID HOLDER / Cooling holder cryogen: NITROGEN |
Image recording | Film or detector model: GATAN K3 (6k x 4k) / Average electron dose: 53.8 e/Å2 |
Experimental equipment | ![]() Model: Titan Krios / Image courtesy: FEI Company |