+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-34917 | |||||||||
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Title | Structure of CXCR3 complexed with antagonist SCH546738 | |||||||||
Map data | ||||||||||
Sample |
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Keywords | G protein coupled receptor / chemokine receptor / CXCR3 / SCH546738 / complex / SIGNALING PROTEIN | |||||||||
Function / homology | Function and homology information dynorphin receptor activity / response to acrylamide / regulation of saliva secretion / regulation of leukocyte migration / sensory perception of temperature stimulus / positive regulation of eating behavior / C-X-C chemokine binding / adenylate cyclase-inhibiting opioid receptor signaling pathway / chemokine binding / G protein-coupled opioid receptor activity ...dynorphin receptor activity / response to acrylamide / regulation of saliva secretion / regulation of leukocyte migration / sensory perception of temperature stimulus / positive regulation of eating behavior / C-X-C chemokine binding / adenylate cyclase-inhibiting opioid receptor signaling pathway / chemokine binding / G protein-coupled opioid receptor activity / 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 / C-C chemokine receptor activity / sensory perception / positive regulation of potassium ion transmembrane transport / conditioned place preference / C-C chemokine binding / positive regulation of chemotaxis / negative regulation of execution phase of apoptosis / maternal behavior / receptor serine/threonine kinase binding / neuropeptide 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 / neuropeptide signaling pathway / estrous cycle / regulation of cell adhesion / negative regulation of angiogenesis / MECP2 regulates neuronal receptors and channels / axon terminus / sensory perception of pain / T-tubule / adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway / Peptide ligand-binding receptors / cell chemotaxis / positive regulation of release of sequestered calcium ion into cytosol / sarcoplasmic reticulum / locomotory behavior / cellular response to glucose stimulus / electron transport chain / calcium-mediated signaling / 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 / signaling receptor activity / presynaptic membrane / phospholipase C-activating G protein-coupled receptor signaling pathway / positive regulation of cytosolic calcium ion concentration / G alpha (i) signalling events / cellular response to lipopolysaccharide / chemical synaptic transmission / postsynaptic membrane / perikaryon / angiogenesis / response to ethanol / defense response to virus / periplasmic space / cell surface receptor signaling pathway / electron transfer activity / cell adhesion / neuron projection / inflammatory response / iron ion binding / immune response / G protein-coupled receptor signaling pathway / external side of plasma membrane / positive regulation of cell population proliferation / dendrite / heme binding / apoptotic process / cell surface / positive regulation of transcription by RNA polymerase II / mitochondrion / nucleoplasm / membrane / plasma membrane / cytoplasm / cytosol Similarity search - Function | |||||||||
Biological species | Homo sapiens (human) / Lama glama (llama) | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 3.6 Å | |||||||||
Authors | Jiao HZ / Hu HL | |||||||||
Funding support | China, 1 items
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Citation | Journal: Nat Struct Mol Biol / Year: 2024 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 | emd_34917.map.gz | 78.8 MB | EMDB map data format | |
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Header (meta data) | emd-34917-v30.xml emd-34917.xml | 18.2 KB 18.2 KB | Display Display | EMDB header |
FSC (resolution estimation) | emd_34917_fsc.xml | 9.3 KB | Display | FSC data file |
Images | emd_34917.png | 88.3 KB | ||
Filedesc metadata | emd-34917.cif.gz | 6.1 KB | ||
Others | emd_34917_additional_1.map.gz emd_34917_half_map_1.map.gz emd_34917_half_map_2.map.gz | 40.9 MB 77.7 MB 77.7 MB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-34917 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-34917 | HTTPS FTP |
-Validation report
Summary document | emd_34917_validation.pdf.gz | 779.1 KB | Display | EMDB validaton report |
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Full document | emd_34917_full_validation.pdf.gz | 778.7 KB | Display | |
Data in XML | emd_34917_validation.xml.gz | 17.5 KB | Display | |
Data in CIF | emd_34917_validation.cif.gz | 22.3 KB | Display | |
Arichive directory | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-34917 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-34917 | HTTPS FTP |
-Related structure data
Related structure data | 8hnnMC 8hnkC 8hnlC 8hnmC M: atomic model generated by this map C: citing same article (ref.) |
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Similar structure data | Similarity search - Function & homologyF&H Search |
-Links
EMDB pages | EMDB (EBI/PDBe) / EMDataResource |
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Related items in Molecule of the Month |
-Map
File | Download / File: emd_34917.map.gz / Format: CCP4 / Size: 83.7 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||
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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
File | emd_34917_additional_1.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Half map: #2
File | emd_34917_half_map_1.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Half map: #1
File | emd_34917_half_map_2.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-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: Homo sapiens (human) |
-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: Lama glama (llama) |
Molecular weight | Theoretical: 18.665906 KDa |
Recombinant expression | Organism: Spodoptera frugiperda (fall armyworm) |
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: Homo sapiens (human) |
Molecular weight | Theoretical: 56.327051 KDa |
Recombinant expression | Organism: Spodoptera frugiperda (fall armyworm) |
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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Processing | single particle reconstruction |
Aggregation state | particle |
-Sample preparation
Concentration | 5.0 mg/mL |
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Buffer | pH: 7.5 |
Vitrification | Cryogen name: ETHANE / Chamber humidity: 100 % |
-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: FIELD EMISSION GUN |
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 |