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Open data
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Basic information
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Title | Structure of CXCR3 complexed with antagonist SCH546738 | |||||||||
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![]() | G protein coupled receptor / chemokine receptor / CXCR3 / SCH546738 / complex / SIGNALING PROTEIN | |||||||||
Function / homology | ![]() dynorphin receptor activity / response to acrylamide / regulation of saliva secretion / regulation of leukocyte migration / sensory perception of temperature stimulus / positive regulation of eating behavior / adenylate cyclase-inhibiting opioid receptor signaling pathway / C-X-C chemokine binding / G protein-coupled opioid receptor activity / chemokine binding ...dynorphin receptor activity / response to acrylamide / regulation of saliva secretion / regulation of leukocyte migration / sensory perception of temperature stimulus / positive regulation of eating behavior / adenylate cyclase-inhibiting opioid receptor signaling pathway / C-X-C chemokine binding / G protein-coupled opioid receptor activity / chemokine binding / negative regulation of luteinizing hormone secretion / C-X-C chemokine receptor activity / G protein-coupled opioid receptor signaling pathway / chemokine receptor activity / positive regulation of dopamine secretion / sensory perception / positive regulation of potassium ion transmembrane transport / conditioned place preference / positive regulation of chemotaxis / C-C chemokine receptor activity / maternal behavior / negative regulation of execution phase of apoptosis / C-C chemokine binding / neuropeptide binding / receptor serine/threonine kinase binding / Chemokine receptors bind chemokines / positive regulation of p38MAPK cascade / eating behavior / positive regulation of execution phase of apoptosis / negative regulation of endothelial cell proliferation / behavioral response to cocaine / estrous cycle / neuropeptide signaling pathway / regulation of cell adhesion / axon terminus / MECP2 regulates neuronal receptors and channels / sensory perception of pain / T-tubule / adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway / Peptide ligand-binding receptors / negative regulation of angiogenesis / cell chemotaxis / positive regulation of release of sequestered calcium ion into cytosol / sarcoplasmic reticulum / locomotory behavior / calcium-mediated signaling / cellular response to glucose stimulus / electron transport chain / response to nicotine / response to insulin / adenylate cyclase-activating G protein-coupled receptor signaling pathway / synaptic vesicle membrane / response to estrogen / positive regulation of angiogenesis / chemotaxis / phospholipase C-activating G protein-coupled receptor signaling pathway / presynaptic membrane / signaling receptor activity / G alpha (i) signalling events / positive regulation of cytosolic calcium ion concentration / chemical synaptic transmission / postsynaptic membrane / cellular response to lipopolysaccharide / perikaryon / angiogenesis / response to ethanol / defense response to virus / periplasmic space / electron transfer activity / cell surface receptor signaling pathway / cell adhesion / inflammatory response / neuron projection / iron ion binding / immune response / G protein-coupled receptor signaling pathway / external side of plasma membrane / apoptotic process / dendrite / heme binding / positive regulation of cell population proliferation / cell surface / positive regulation of transcription by RNA polymerase II / mitochondrion / nucleoplasm / membrane / plasma membrane / cytoplasm / cytosol Similarity search - Function | |||||||||
Biological species | ![]() ![]() ![]() | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 3.6 Å | |||||||||
![]() | Jiao HZ / Hu HL | |||||||||
Funding support | ![]()
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![]() | ![]() Title: Structural insights into the activation and inhibition of CXC chemokine receptor 3. Authors: Haizhan Jiao / Bin Pang / Aijun Liu / Qiang Chen / Qi Pan / Xiankun Wang / Yunong Xu / Ying-Chih Chiang / Ruobing Ren / Hongli Hu / ![]() Abstract: The chemotaxis of CD4 type 1 helper cells and CD8 cytotoxic lymphocytes, guided by interferon-inducible CXC chemokine 9-11 (CXCL9-11) and CXC chemokine receptor 3 (CXCR3), plays a critical role in ...The chemotaxis of CD4 type 1 helper cells and CD8 cytotoxic lymphocytes, guided by interferon-inducible CXC chemokine 9-11 (CXCL9-11) and CXC chemokine receptor 3 (CXCR3), plays a critical role in type 1 immunity. Here we determined the structures of human CXCR3-DNG complexes activated by chemokine CXCL11, peptidomimetic agonist PS372424 and biaryl-type agonist VUF11222, and the structure of inactive CXCR3 bound to noncompetitive antagonist SCH546738. Structural analysis revealed that PS372424 shares a similar orthosteric binding pocket to the N terminus of CXCL11, while VUF11222 buries deeper and activates the receptor in a distinct manner. We showed an allosteric binding site between TM5 and TM6, accommodating SCH546738 in the inactive CXCR3. SCH546738 may restrain the receptor at an inactive state by preventing the repacking of TM5 and TM6. By revealing the binding patterns and the pharmacological properties of the four modulators, we present the activation mechanisms of CXCR3 and provide insights for future drug development. | |||||||||
History |
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Structure visualization
Supplemental images |
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Downloads & links
-EMDB archive
Map data | ![]() | 78.8 MB | ![]() | |
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Header (meta data) | ![]() ![]() | 18.2 KB 18.2 KB | Display Display | ![]() |
FSC (resolution estimation) | ![]() | 9.3 KB | Display | ![]() |
Images | ![]() | 88.3 KB | ||
Filedesc metadata | ![]() | 6.1 KB | ||
Others | ![]() ![]() ![]() | 40.9 MB 77.7 MB 77.7 MB | ||
Archive directory | ![]() ![]() | HTTPS FTP |
-Validation report
Summary document | ![]() | 779.1 KB | Display | ![]() |
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Full document | ![]() | 778.7 KB | Display | |
Data in XML | ![]() | 17.5 KB | Display | |
Data in CIF | ![]() | 22.3 KB | Display | |
Arichive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 8hnnMC ![]() 8hnkC ![]() 8hnlC ![]() 8hnmC 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: 0.85 Å | ||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||
Details | EMDB XML:
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-Supplemental data
-Additional map: #1
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Density Histograms |
-Half map: #2
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Density Histograms |
-Half map: #1
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Sample components
-Entire : CXCR3-KOR-SCH546738-Nb6
Entire | Name: CXCR3-KOR-SCH546738-Nb6 |
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Components |
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-Supramolecule #1: CXCR3-KOR-SCH546738-Nb6
Supramolecule | Name: CXCR3-KOR-SCH546738-Nb6 / type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1-#2 |
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Source (natural) | Organism: ![]() |
-Macromolecule #1: Nb6
Macromolecule | Name: Nb6 / type: protein_or_peptide / ID: 1 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() ![]() |
Molecular weight | Theoretical: 18.665906 KDa |
Recombinant expression | Organism: ![]() ![]() |
Sequence | String: MLLVNQSHQG FNKEHTSKMV SAIVLYVLLA AAAHSAFAMA QVQLQESGGG LVQAGESLRL SCAASGTIFR LYDMGWYRRV SGNQRELVA SITSGGSTKY GDSVKGRFTI SRDNAKNTVY LQMSSLKPED TAVYYCNAEY RTGIWEELLD GWGQGTQVTV S SHHHHHHH H |
-Macromolecule #2: Soluble cytochrome b562,C-X-C chemokine receptor type 3,Kappa-typ...
Macromolecule | Name: Soluble cytochrome b562,C-X-C chemokine receptor type 3,Kappa-type opioid receptor type: protein_or_peptide / ID: 2 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() |
Molecular weight | Theoretical: 56.327051 KDa |
Recombinant expression | Organism: ![]() ![]() |
Sequence | String: MKTIIALSYI FCLVFADYKD DDDKGSADLE DNWETLNDNL KVIEKADNAA QVKDALTKMR AAALDAQKAT PPKLEDKSPD SPEMKDFRH GFDILVGQID DALKLANEGK VKEAQAAAEQ LKTTRNAYIQ KYLLVPRGSM VLEVSDHQVL NDAEVAALLE N FSSSYDYG ...String: MKTIIALSYI FCLVFADYKD DDDKGSADLE DNWETLNDNL KVIEKADNAA QVKDALTKMR AAALDAQKAT PPKLEDKSPD SPEMKDFRH GFDILVGQID DALKLANEGK VKEAQAAAEQ LKTTRNAYIQ KYLLVPRGSM VLEVSDHQVL NDAEVAALLE N FSSSYDYG ENESDSCCTS PPCPQDFSLN FDRAFLPALY SLLFLLGLLG NGAVAAVLLS RRTALSSTDT FLLHLAVADT LL VLTLPLW AVDAAVQWVF GSGLCKVAGA LFNINFYAGA LLLACISFDR YLNIVHATQL YRRGPPARVT LTCLAVWGLC LLF ALPDFI FLSAHHDERL NATHCQYNFP QVGRTALRVL QLVAGFLLPL LVMAYCYAHI LARLKSVRLL SGSREKDRNL RRIT RLVVV VVVAFALCWT PYHLVVLVDI LMDLGALARN CGRESRVDVA KSVTSGLGYM HCCLNPLLYA FVGVKFRERM WMLLL RLGC PNQRGLQRQP SSSRRDSSWS ETS UniProtKB: Soluble cytochrome b562, C-X-C chemokine receptor type 3, Kappa-type opioid receptor, C-X-C chemokine receptor type 3 |
-Macromolecule #3: 3-azanyl-6-chloranyl-5-[(3S)-4-[1-[(4-chlorophenyl)methyl]piperid...
Macromolecule | Name: 3-azanyl-6-chloranyl-5-[(3S)-4-[1-[(4-chlorophenyl)methyl]piperidin-4-yl]-3-ethyl-piperazin-1-yl]pyrazine-2-carboxamide type: ligand / ID: 3 / Number of copies: 1 / Formula: 43I |
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Molecular weight | Theoretical: 492.445 Da |
Chemical component information | ![]() ChemComp-43I: |
-Macromolecule #4: CHOLESTEROL
Macromolecule | Name: CHOLESTEROL / type: ligand / ID: 4 / Number of copies: 1 / Formula: CLR |
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Molecular weight | Theoretical: 386.654 Da |
Chemical component information | ![]() ChemComp-CLR: |
-Experimental details
-Structure determination
Method | cryo EM |
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![]() | single particle reconstruction |
Aggregation state | particle |
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Sample preparation
Concentration | 5.0 mg/mL |
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Buffer | pH: 7.5 |
Vitrification | Cryogen name: ETHANE / Chamber humidity: 100 % |
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Electron microscopy
Microscope | FEI TITAN KRIOS |
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Specialist optics | Energy filter - Name: GIF Bioquantum / Energy filter - Slit width: 20 eV |
Image recording | Film or detector model: GATAN K3 BIOQUANTUM (6k x 4k) / Average electron dose: 53.43 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: 2.0 µm / Nominal defocus min: 1.5 µm / Nominal magnification: 105000 |
Experimental equipment | ![]() Model: Titan Krios / Image courtesy: FEI Company |