+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-34914 | |||||||||
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Title | CXCR3-DNGi complex activated by CXCL11 | |||||||||
Map data | sharpened map (Phenix.AtuoSharpen) | |||||||||
Sample |
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Keywords | G protein coupled receptor / chemokine receptor / CXCR3 / CXCL11 / complex / SIGNALING PROTEIN | |||||||||
Function / homology | Function and homology information Oplophorus-luciferin 2-monooxygenase / Oplophorus-luciferin 2-monooxygenase activity / CXCR3 chemokine receptor binding / regulation of leukocyte migration / C-X-C chemokine binding / chemokine binding / C-X-C chemokine receptor activity / chemokine receptor activity / CXCR chemokine receptor binding / C-C chemokine receptor activity ...Oplophorus-luciferin 2-monooxygenase / Oplophorus-luciferin 2-monooxygenase activity / CXCR3 chemokine receptor binding / regulation of leukocyte migration / C-X-C chemokine binding / chemokine binding / C-X-C chemokine receptor activity / chemokine receptor activity / CXCR chemokine receptor binding / C-C chemokine receptor activity / C-C chemokine binding / positive regulation of chemotaxis / T cell chemotaxis / negative regulation of execution phase of apoptosis / chemokine-mediated signaling pathway / Chemokine receptors bind chemokines / chemokine activity / negative regulation of endothelial cell proliferation / positive regulation of execution phase of apoptosis / T cell migration / D2 dopamine receptor binding / Adenylate cyclase inhibitory pathway / positive regulation of protein localization to cell cortex / regulation of cell adhesion / regulation of cAMP-mediated signaling / G protein-coupled serotonin receptor binding / cellular response to forskolin / regulation of mitotic spindle organization / neutrophil chemotaxis / adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway / negative regulation of angiogenesis / bioluminescence / cell chemotaxis / positive regulation of release of sequestered calcium ion into cytosol / Regulation of insulin secretion / G protein-coupled receptor binding / calcium-mediated signaling / electron transport chain / G-protein beta/gamma-subunit complex binding / adenylate cyclase-modulating G protein-coupled receptor signaling pathway / Olfactory Signaling Pathway / Activation of the phototransduction cascade / adenylate cyclase-activating G protein-coupled receptor signaling pathway / G beta:gamma signalling through PLC beta / Presynaptic function of Kainate receptors / Thromboxane signalling through TP receptor / G protein-coupled acetylcholine receptor signaling pathway / G-protein activation / Activation of G protein gated Potassium channels / Inhibition of voltage gated Ca2+ channels via Gbeta/gamma subunits / Prostacyclin signalling through prostacyclin receptor / Glucagon signaling in metabolic regulation / G beta:gamma signalling through CDC42 / response to peptide hormone / G beta:gamma signalling through BTK / ADP signalling through P2Y purinoceptor 12 / Sensory perception of sweet, bitter, and umami (glutamate) taste / Synthesis, secretion, and inactivation of Glucagon-like Peptide-1 (GLP-1) / photoreceptor disc membrane / Glucagon-type ligand receptors / Adrenaline,noradrenaline inhibits insulin secretion / Vasopressin regulates renal water homeostasis via Aquaporins / G alpha (z) signalling events / Glucagon-like Peptide-1 (GLP1) regulates insulin secretion / ADORA2B mediated anti-inflammatory cytokines production / cellular response to catecholamine stimulus / positive regulation of angiogenesis / sensory perception of taste / ADP signalling through P2Y purinoceptor 1 / G beta:gamma signalling through PI3Kgamma / adenylate cyclase-activating dopamine receptor signaling pathway / Cooperation of PDCL (PhLP1) and TRiC/CCT in G-protein beta folding / chemotaxis / GPER1 signaling / GDP binding / cellular response to prostaglandin E stimulus / G-protein beta-subunit binding / antimicrobial humoral immune response mediated by antimicrobial peptide / Inactivation, recovery and regulation of the phototransduction cascade / heterotrimeric G-protein complex / G alpha (12/13) signalling events / extracellular vesicle / signaling receptor complex adaptor activity / Thrombin signalling through proteinase activated receptors (PARs) / cell-cell signaling / GTPase binding / heparin binding / retina development in camera-type eye / signaling receptor activity / Ca2+ pathway / regulation of cell population proliferation / cell cortex / phospholipase C-activating G protein-coupled receptor signaling pathway / positive regulation of cytosolic calcium ion concentration / midbody / G alpha (i) signalling events / fibroblast proliferation / G alpha (s) signalling events / cellular response to lipopolysaccharide / Hydrolases; Acting on acid anhydrides; Acting on GTP to facilitate cellular and subcellular movement Similarity search - Function | |||||||||
Biological species | Homo sapiens (human) / Oplophorus gracilirostris (crustacean) | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 3.01 Å | |||||||||
Authors | Jiao HZ / Hu HL | |||||||||
Funding support | China, 2 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_34914.map.gz | 65.7 MB | EMDB map data format | |
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Header (meta data) | emd-34914-v30.xml emd-34914.xml | 25.8 KB 25.8 KB | Display Display | EMDB header |
Images | emd_34914.png | 98.8 KB | ||
Filedesc metadata | emd-34914.cif.gz | 7.3 KB | ||
Others | emd_34914_additional_1.map.gz emd_34914_additional_2.map.gz emd_34914_half_map_1.map.gz emd_34914_half_map_2.map.gz | 64.9 MB 41.2 MB 65.3 MB 65.3 MB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-34914 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-34914 | HTTPS FTP |
-Validation report
Summary document | emd_34914_validation.pdf.gz | 780.1 KB | Display | EMDB validaton report |
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Full document | emd_34914_full_validation.pdf.gz | 779.7 KB | Display | |
Data in XML | emd_34914_validation.xml.gz | 12.9 KB | Display | |
Data in CIF | emd_34914_validation.cif.gz | 15.1 KB | Display | |
Arichive directory | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-34914 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-34914 | HTTPS FTP |
-Related structure data
Related structure data | 8hnkMC 8hnlC 8hnmC 8hnnC 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_34914.map.gz / Format: CCP4 / Size: 83.7 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||
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Annotation | sharpened map (Phenix.AtuoSharpen) | ||||||||||||||||||||||||||||||||||||
Projections & slices | Image control
Images are generated by Spider. | ||||||||||||||||||||||||||||||||||||
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: unsharpened map (Relion.AutoRefine)
File | emd_34914_additional_1.map | ||||||||||||
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Annotation | unsharpened map (Relion.AutoRefine) | ||||||||||||
Projections & Slices |
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Density Histograms |
-Additional map: scaled map (CCPEM.LocalScale)
File | emd_34914_additional_2.map | ||||||||||||
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Annotation | scaled map (CCPEM.LocalScale) | ||||||||||||
Projections & Slices |
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Density Histograms |
-Half map: half map (Relion.AutoRefine)
File | emd_34914_half_map_1.map | ||||||||||||
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Annotation | half map (Relion.AutoRefine) | ||||||||||||
Projections & Slices |
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Density Histograms |
-Half map: half map (Relion.AutoRefine)
File | emd_34914_half_map_2.map | ||||||||||||
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Annotation | half map (Relion.AutoRefine) | ||||||||||||
Projections & Slices |
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Density Histograms |
-Sample components
-Entire : CXCR3-CXCL11-DNGi-scFv16
Entire | Name: CXCR3-CXCL11-DNGi-scFv16 |
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Components |
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-Supramolecule #1: CXCR3-CXCL11-DNGi-scFv16
Supramolecule | Name: CXCR3-CXCL11-DNGi-scFv16 / type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1-#6 |
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Source (natural) | Organism: Homo sapiens (human) |
-Macromolecule #1: Guanine nucleotide-binding protein G(i) subunit alpha-1
Macromolecule | Name: Guanine nucleotide-binding protein G(i) subunit alpha-1 type: protein_or_peptide / ID: 1 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: Homo sapiens (human) |
Molecular weight | Theoretical: 40.445059 KDa |
Recombinant expression | Organism: Spodoptera frugiperda (fall armyworm) |
Sequence | String: MGCTLSAEDK AAVERSKMID RNLREDGEKA AREVKLLLLG AGESGKSTIV KQMKIIHEAG YSEEECKQYK AVVYSNTIQS IIAIIRAMG RLKIDFGDSA RADDARQLFV LAGAAEEGFM TAELAGVIKR LWKDSGVQAC FNRSREYQLN DSAAYYLNDL D RIAQPNYI ...String: MGCTLSAEDK AAVERSKMID RNLREDGEKA AREVKLLLLG AGESGKSTIV KQMKIIHEAG YSEEECKQYK AVVYSNTIQS IIAIIRAMG RLKIDFGDSA RADDARQLFV LAGAAEEGFM TAELAGVIKR LWKDSGVQAC FNRSREYQLN DSAAYYLNDL D RIAQPNYI PTQQDVLRTR VKTTGIVETH FTFKDLHFKM FDVGAQRSER KKWIHCFEGV TAIIFCVALS DYDLVLAEDE EM NRMHESM KLFDSICNNK WFTDTSIILF LNKKDLFEEK IKKSPLTICY PEYAGSNTYE EAAAYIQCQF EDLNKRKDTK EIY THFTCS TDTKNVQFVF DAVTDVIIKN NLKDCGLF UniProtKB: Guanine nucleotide-binding protein G(i) subunit alpha-1 |
-Macromolecule #2: Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1
Macromolecule | Name: Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1 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: 42.005895 KDa |
Recombinant expression | Organism: Spodoptera frugiperda (fall armyworm) |
Sequence | String: HHHHHHHHHH LEVLFQGPGS SGSELDQLRQ EAEQLKNQIR DARKACADAT LSQITNNIDP VGRIQMRTRR TLRGHLAKIY AMHWGTDSR LLVSASQDGK LIIWDSYTTN KVHAIPLRSS WVMTCAYAPS GNYVACGGLD NICSIYNLKT REGNVRVSRE L AGHTGYLS ...String: HHHHHHHHHH LEVLFQGPGS SGSELDQLRQ EAEQLKNQIR DARKACADAT LSQITNNIDP VGRIQMRTRR TLRGHLAKIY AMHWGTDSR LLVSASQDGK LIIWDSYTTN KVHAIPLRSS WVMTCAYAPS GNYVACGGLD NICSIYNLKT REGNVRVSRE L AGHTGYLS CCRFLDDNQI VTSSGDTTCA LWDIETGQQT TTFTGHTGDV MSLSLAPDTR LFVSGACDAS AKLWDVREGM CR QTFTGHE SDINAICFFP NGNAFATGSD DATCRLFDLR ADQELMTYSH DNIICGITSV SFSKSGRLLL AGYDDFNCNV WDA LKADRA GVLAGHDNRV SCLGVTDDGM AVATGSWDSF LKIWNGASGA SGASGASVSG WRLFKKIS UniProtKB: Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1 |
-Macromolecule #3: Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2
Macromolecule | Name: Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2 type: protein_or_peptide / ID: 3 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: Homo sapiens (human) |
Molecular weight | Theoretical: 7.861143 KDa |
Recombinant expression | Organism: Spodoptera frugiperda (fall armyworm) |
Sequence | String: MASNNTASIA QARKLVEQLK MEANIDRIKV SKAAADLMAY CEAHAKEDPL LTPVPASENP FREKKFFCAI L UniProtKB: Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2 |
-Macromolecule #4: Soluble cytochrome b562,C-X-C chemokine receptor type 3,Oplophoru...
Macromolecule | Name: Soluble cytochrome b562,C-X-C chemokine receptor type 3,Oplophorus-luciferin 2-monooxygenase catalytic subunit type: protein_or_peptide / ID: 4 / Number of copies: 1 / Enantiomer: LEVO / EC number: Oplophorus-luciferin 2-monooxygenase |
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Source (natural) | Organism: Oplophorus gracilirostris (crustacean) |
Molecular weight | Theoretical: 72.918008 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 LAVLLVSRGQ RRLRAMRLVV VVVV AFALC WTPYHLVVLV DILMDLGALA RNCGRESRVD VAKSVTSGLG YMHCCLNPLL YAFVGVKFRE RMWMLLLRLG CPNQR GLQR QPSSSRRDSS WSETSVFTLE DFVGDWEQTA AYNLDQVLEQ GGVSSLLQNL AVSVTPIQRI VRSGENALKI DIHVII PYE GLSADQMAQI EEVFKVVYPV DDHHFKVILP YGTLVIDGVT PNMLNYFGRP YEGIAVFDGK KITVTGTLWN GNKIIDE RL ITPDGSMLFR VTINS UniProtKB: Soluble cytochrome b562, C-X-C chemokine receptor type 3, Oplophorus-luciferin 2-monooxygenase catalytic subunit |
-Macromolecule #5: C-X-C motif chemokine 11
Macromolecule | Name: C-X-C motif chemokine 11 / type: protein_or_peptide / ID: 5 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: Homo sapiens (human) |
Molecular weight | Theoretical: 11.764127 KDa |
Recombinant expression | Organism: Spodoptera frugiperda (fall armyworm) |
Sequence | String: MSVKGMAIAL AVILCATVVQ GFPMFKRGRC LCIGPGVKAV KVADIEKASI MYPSNNCDKI EVIITLKENK GQRCLNPKSK QARLIIKKV ERKNFHHHHH HHHHH UniProtKB: C-X-C motif chemokine 11 |
-Macromolecule #6: single-chain variable fragment scFv16
Macromolecule | Name: single-chain variable fragment scFv16 / type: protein_or_peptide / ID: 6 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: Homo sapiens (human) |
Molecular weight | Theoretical: 27.784896 KDa |
Recombinant expression | Organism: Spodoptera frugiperda (fall armyworm) |
Sequence | String: DVQLVESGGG LVQPGGSRKL SCSASGFAFS SFGMHWVRQA PEKGLEWVAY ISSGSGTIYY ADTVKGRFTI SRDDPKNTLF LQMTSLRSE DTAMYYCVRS IYYYGSSPFD FWGQGTTLTV SSGGGGSGGG GSGGGGSDIV MTQATSSVPV TPGESVSISC R SSKSLLHS ...String: DVQLVESGGG LVQPGGSRKL SCSASGFAFS SFGMHWVRQA PEKGLEWVAY ISSGSGTIYY ADTVKGRFTI SRDDPKNTLF LQMTSLRSE DTAMYYCVRS IYYYGSSPFD FWGQGTTLTV SSGGGGSGGG GSGGGGSDIV MTQATSSVPV TPGESVSISC R SSKSLLHS NGNTYLYWFL QRPGQSPQLL IYRMSNLASG VPDRFSGSGS GTAFTLTISR LEAEDVGVYY CMQHLEYPLT FG AGTKLEL KAAAHHHHHH HH |
-Macromolecule #7: CHOLESTEROL
Macromolecule | Name: CHOLESTEROL / type: ligand / ID: 7 / Number of copies: 2 / 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: 56.25 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: 1.8 µm / Nominal defocus min: 1.2 µm / Nominal magnification: 105000 |
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |
-Image processing
Startup model | Type of model: EMDB MAP EMDB ID: |
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Final reconstruction | Resolution.type: BY AUTHOR / Resolution: 3.01 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 96877 |
Initial angle assignment | Type: RANDOM ASSIGNMENT |
Final angle assignment | Type: PROJECTION MATCHING |