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Open data
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Basic information
| Entry | ![]() | |||||||||
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| Title | Composite map of CXCL10-CXCR3-Gi-scFv16 | |||||||||
Map data | Composite map of CXCL10-CXCR3-Gi-scFv16 | |||||||||
Sample |
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Keywords | GPCR / chemokine receptor / MEMBRANE PROTEIN | |||||||||
| Function / homology | Function and homology informationregulation of T cell chemotaxis / CXCR3 chemokine receptor binding / regulation of leukocyte migration / chemokine binding / C-X-C chemokine binding / regulation of endothelial tube morphogenesis / Differentiation of naive CD4+ T cells to T helper 1 cells (Th1 cells) / cellular response to interleukin-17 / chemokine receptor activity / CXCR chemokine receptor binding ...regulation of T cell chemotaxis / CXCR3 chemokine receptor binding / regulation of leukocyte migration / chemokine binding / C-X-C chemokine binding / regulation of endothelial tube morphogenesis / Differentiation of naive CD4+ T cells to T helper 1 cells (Th1 cells) / cellular response to interleukin-17 / chemokine receptor activity / CXCR chemokine receptor binding / C-X-C chemokine receptor activity / cAMP-dependent protein kinase regulator activity / response to auditory stimulus / positive regulation of chemotaxis / T cell chemotaxis / negative regulation of execution phase of apoptosis / C-C chemokine binding / C-C chemokine receptor activity / positive regulation of monocyte chemotaxis / response to vitamin D / endothelial cell activation / chemokine activity / Chemokine receptors bind chemokines / blood circulation / muscle organ development / negative regulation of endothelial cell proliferation / chemoattractant activity / Interleukin-10 signaling / positive regulation of execution phase of apoptosis / regulation of cell adhesion / positive regulation of T cell migration / neutrophil chemotaxis / regulation of eating behavior / adenylate cyclase inhibitor activity / T cell migration / response to gamma radiation / positive regulation of protein localization to cell cortex / positive regulation of relaxation of smooth muscle / Adenylate cyclase inhibitory pathway / D2 dopamine receptor binding / negative regulation of angiogenesis / adenylate cyclase-inhibiting serotonin receptor signaling pathway / G protein-coupled serotonin receptor binding / positive regulation of release of sequestered calcium ion into cytosol / cellular response to forskolin / bioluminescence / antiviral innate immune response / regulation of mitotic spindle organization / calcium-mediated signaling / mast cell degranulation / chemokine-mediated signaling pathway / cell chemotaxis / generation of precursor metabolites and energy / neuropeptide signaling pathway / Regulation of insulin secretion / cellular response to virus / response to prostaglandin E / positive regulation of cholesterol biosynthetic process / G protein-coupled receptor binding / response to peptide hormone / chemotaxis / positive regulation of angiogenesis / G-protein beta/gamma-subunit complex binding / adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway / adenylate cyclase-modulating G protein-coupled receptor signaling pathway / Olfactory Signaling Pathway / Activation of the phototransduction cascade / G protein-coupled acetylcholine receptor signaling pathway / G beta:gamma signalling through PLC beta / Presynaptic function of Kainate receptors / Thromboxane signalling through TP receptor / Activation of G protein gated Potassium channels / Inhibition of voltage gated Ca2+ channels via Gbeta/gamma subunits / G-protein activation / Glucagon signaling in metabolic regulation / G beta:gamma signalling through CDC42 / Prostacyclin signalling through prostacyclin receptor / Synthesis, secretion, and inactivation of Glucagon-like Peptide-1 (GLP-1) / GDP binding / G beta:gamma signalling through BTK / photoreceptor disc membrane / ADP signalling through P2Y purinoceptor 12 / Glucagon-type ligand receptors / Sensory perception of sweet, bitter, and umami (glutamate) taste / Adrenaline,noradrenaline inhibits insulin secretion / regulation of cell population proliferation / cell-cell signaling / Vasopressin regulates renal water homeostasis via Aquaporins / Glucagon-like Peptide-1 (GLP1) regulates insulin secretion / G alpha (z) signalling events / cellular response to catecholamine stimulus / ADP signalling through P2Y purinoceptor 1 / G beta:gamma signalling through PI3Kgamma / ADORA2B mediated anti-inflammatory cytokines production / adenylate cyclase-activating dopamine receptor signaling pathway / heparin binding / cellular response to prostaglandin E stimulus / Cooperation of PDCL (PhLP1) and TRiC/CCT in G-protein beta folding / cellular response to heat / GPER1 signaling Similarity search - Function | |||||||||
| Biological species | Homo sapiens (human) / ![]() | |||||||||
| Method | single particle reconstruction / cryo EM / Resolution: 3.1 Å | |||||||||
Authors | Sun D / Masureel M / Johnson M | |||||||||
| Funding support | 1 items
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Citation | Journal: Sci Adv / Year: 2026Title: Molecular basis of CXC chemokine receptor 3 ligand multispecificity. Authors: Alexandre Bouyssou / Dawei Sun / Tricia Zhou / Shannon Smith / Hoangdung Ho / Matthew Johnson / Caleigh Azumaya / Sigrid Noreng / Peter Liu / Shu Ti / Prajakta Joshi / Christine Tam / Ying ...Authors: Alexandre Bouyssou / Dawei Sun / Tricia Zhou / Shannon Smith / Hoangdung Ho / Matthew Johnson / Caleigh Azumaya / Sigrid Noreng / Peter Liu / Shu Ti / Prajakta Joshi / Christine Tam / Ying Yang / Eric Janezic / Laëtitia Comps-Agrar / Matthieu Masureel / ![]() Abstract: C-X-C motif chemokine receptor 3 (CXCR3) is essential for immune cell functions and pivotal in T helper 1 cell infiltration in autoimmune and chronic inflammatory diseases and in tumor proliferation ...C-X-C motif chemokine receptor 3 (CXCR3) is essential for immune cell functions and pivotal in T helper 1 cell infiltration in autoimmune and chronic inflammatory diseases and in tumor proliferation and metastasis, but the mechanisms by which the endogenous ligands CXCL9, CXCL10, and CXCL11 differentially recognize and activate CXCR3 are not fully understood. Here, we present cryo-electron microscopy structures of all three chemokine-CXCR3-G complexes, complemented by cell binding studies and functional mutagenesis data. We systematically compare the pharmacological and interaction profiles of CXCL9, CXCL10, and CXCL11 to rationalize their varying efficacies and potencies and to reveal the critical role of the membrane-distal CXCR3 N terminus in ligand binding and signaling. Using chimeric chemokines and molecular dynamics, we reveal the signaling plasticity of chemokine ligands and signaling determinants. Together, these insights enable us to propose a multimodal binding and activation framework that explains CXCR3 chemokine ligand multispecificity and signaling versatility and offer tools to interrogate and modulate CXCR3 biology. | |||||||||
| History |
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Structure visualization
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Downloads & links
-EMDB archive
| Map data | emd_71080.map.gz | 31.3 MB | EMDB map data format | |
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| Header (meta data) | emd-71080-v30.xml emd-71080.xml | 18.5 KB 18.5 KB | Display Display | EMDB header |
| Images | emd_71080.png | 71.9 KB | ||
| Filedesc metadata | emd-71080.cif.gz | 6.9 KB | ||
| Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-71080 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-71080 | HTTPS FTP |
-Related structure data
| Related structure data | ![]() 9p0lMC ![]() 9p0kC ![]() 9p0mC C: citing same article ( M: atomic model generated by this map |
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| Similar structure data | Similarity search - Function & homology F&H Search |
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Links
| EMDB pages | EMDB (EBI/PDBe) / EMDataResource |
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| Related items in Molecule of the Month |
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Map
| File | Download / File: emd_71080.map.gz / Format: CCP4 / Size: 64 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||
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| Annotation | Composite map of CXCL10-CXCR3-Gi-scFv16 | ||||||||||||||||||||||||||||||||||||
| Projections & slices | Image control
Images are generated by Spider. | ||||||||||||||||||||||||||||||||||||
| Voxel size | X=Y=Z: 1.1422 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 : CXCR3, CXCL10, Gi
| Entire | Name: CXCR3, CXCL10, Gi |
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| Components |
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-Supramolecule #1: CXCR3, CXCL10, Gi
| Supramolecule | Name: CXCR3, CXCL10, Gi / type: complex / ID: 1 / Parent: 0 |
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| Source (natural) | Organism: Homo sapiens (human) |
-Macromolecule #1: C-X-C chemokine receptor type 3,GFP-like fluorescent chromoprotei...
| Macromolecule | Name: C-X-C chemokine receptor type 3,GFP-like fluorescent chromoprotein FP506, related 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: 75.79268 KDa |
| Recombinant expression | Organism: Homo sapiens (human) |
| Sequence | String: MKTIIALSYI FCLVFADYKD DDDKGSENLY FQSGSMVLEV SDHQVLNDAE VAALLENFSS SYDYGENESD SCCTSPPCPQ DFSLNFDRA FLPALYSLLF LLGLLGNGAV AAVLLSRRTA LSSTDTFLLH LAVADTLLVL TLPLWAVDAA VQWVFGSGLC K VAGALFNI ...String: MKTIIALSYI FCLVFADYKD DDDKGSENLY FQSGSMVLEV SDHQVLNDAE VAALLENFSS SYDYGENESD SCCTSPPCPQ DFSLNFDRA FLPALYSLLF LLGLLGNGAV AAVLLSRRTA LSSTDTFLLH LAVADTLLVL TLPLWAVDAA VQWVFGSGLC K VAGALFNI NFYAGALLLA CISFDRYLNI VHATQLYRRG PPARVTLTCL AVWGLCLLFA LPDFIFLSAH HDERLNATHC QY NFPQVGR TALRVLQLVA GFLLPLLVMA YCYAHILAVL LVSRGQRRLR AMRLVVVAVV AFALCWTPYH LVVLVDILMD LGA LARNCG RESRVDVAKS VTSGLGYMHC CLNPLLYAFV GVKFRERMWM LLLRLGCPNQ RGLQRQPSSS RRDSSWSETS EASY SGLGN SLEVLFQGPM VSKGEELFTG VVPILVELDG DVNGHKFSVS GEGEGDATYG KLTLKLICTT GKLPVPWPTL VTTLG YGLQ CFARYPDHMK QHDFFKSAMP EGYVQERTIF FKDDGNYKTR AEVKFEGDTL VNRIELKGID FKEDGNILGH KLEYNY NSH NVYITADKQK NGIKANFKIR HNIEDGGVQL ADHYQQNTPI GDGPVLLPDN HYLSYQSKLS KDPNEKRDHM VLLEFVT AA GITLGMDELY KGSAWSHPQF EKGGGSGGGS GGSAWSHPQF EK UniProtKB: C-X-C chemokine receptor type 3, GFP-like fluorescent chromoprotein FP506, related |
-Macromolecule #2: C-X-C motif chemokine 10
| Macromolecule | Name: C-X-C motif chemokine 10 / 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: 8.663343 KDa |
| Recombinant expression | Organism: ![]() |
| Sequence | String: VPLSRTVRCT CISISNQPVN PRSLEKLEII PASQFCPRVE IIATMKKKGE KRCLNPESKA IKNLLKAVSK ERSKRSP UniProtKB: C-X-C motif chemokine 10 |
-Macromolecule #3: 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: 3 / Number of copies: 1 / Enantiomer: LEVO |
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| Source (natural) | Organism: Homo sapiens (human) |
| Molecular weight | Theoretical: 43.182078 KDa |
| Recombinant expression | Organism: ![]() |
| Sequence | String: MKKHHHHHHH HHHENLYFQG GSMGCTLSAE DKAAVERSKM IDRNLREDGE KAAREVKLLL LGAGESGKST IVKQMKIIHE AGYSEEECK QYKAVVYSNT IQSIIAIIRA MGRLKIDFGD SARADDARQL FVLAGAAEEG FMTAELAGVI KRLWKDSGVQ A CFNRSREY ...String: MKKHHHHHHH HHHENLYFQG GSMGCTLSAE DKAAVERSKM IDRNLREDGE KAAREVKLLL LGAGESGKST IVKQMKIIHE AGYSEEECK QYKAVVYSNT IQSIIAIIRA MGRLKIDFGD SARADDARQL FVLAGAAEEG FMTAELAGVI KRLWKDSGVQ A CFNRSREY QLNDSAAYYL NDLDRIAQPN YIPTQQDVLR TRVKTTGIVE THFTFKDLHF KMFDVGGQRS ERKKWIHCFE GV TAIIFCV ALSDYDLVLA EDEEMNRMHE SMKLFDSICN NKWFTDTSII LFLNKKDLFE EKIKKSPLTI CYPEYAGSNT YEE AAAYIQ CQFEDLNKRK DTKEIYTHFT CATDTKNVQF VFDAVTDVII KNNLKDCGLF UniProtKB: Guanine nucleotide-binding protein G(i) subunit alpha-1 |
-Macromolecule #4: 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: 4 / Number of copies: 1 / Enantiomer: LEVO |
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| Source (natural) | Organism: Homo sapiens (human) |
| Molecular weight | Theoretical: 39.518121 KDa |
| Recombinant expression | Organism: ![]() |
| Sequence | String: MHHHHHHHHG ENLYFQGSSE LDQLRQEAEQ LKNQIRDARK ACADATLSQI TNNIDPVGRI QMRTRRTLRG HLAKIYAMHW GTDSRLLVS ASQDGKLIIW DSYTTNKVHA IPLRSSWVMT CAYAPSGNYV ACGGLDNICS IYNLKTREGN VRVSRELAGH T GYLSCCRF ...String: MHHHHHHHHG ENLYFQGSSE LDQLRQEAEQ LKNQIRDARK ACADATLSQI TNNIDPVGRI QMRTRRTLRG HLAKIYAMHW GTDSRLLVS ASQDGKLIIW DSYTTNKVHA IPLRSSWVMT CAYAPSGNYV ACGGLDNICS IYNLKTREGN VRVSRELAGH T GYLSCCRF LDDNQIVTSS GDTTCALWDI ETGQQTTTFT GHTGDVMSLS LAPDTRLFVS GACDASAKLW DVREGMCRQT FT GHESDIN AICFFPNGNA FATGSDDATC RLFDLRADQE LMTYSHDNII CGITSVSFSK SGRLLLAGYD DFNCNVWDAL KAD RAGVLA GHDNRVSCLG VTDDGMAVAT GSWDSFLKIW N UniProtKB: Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1 |
-Macromolecule #5: 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: 5 / 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: ![]() |
| 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 #6: scFv16
| Macromolecule | Name: scFv16 / type: protein_or_peptide / ID: 6 / Number of copies: 1 / Enantiomer: LEVO |
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| Source (natural) | Organism: ![]() |
| Molecular weight | Theoretical: 28.754949 KDa |
| Recombinant expression | Organism: ![]() |
| Sequence | String: AGSDVQLVES GGGLVQPGGS RKLSCSASGF AFSSFGMHWV RQAPEKGLEW VAYISSGSGT IYYADTVKGR FTISRDDPKN TLFLQMTSL RSEDTAMYYC VRSIYYYGSS PFDFWGQGTT LTVSSGGGSG GGSGGGGSDI VMTQATSSVP VTPGESVSIS C RSSKSLLH ...String: AGSDVQLVES GGGLVQPGGS RKLSCSASGF AFSSFGMHWV RQAPEKGLEW VAYISSGSGT IYYADTVKGR FTISRDDPKN TLFLQMTSL RSEDTAMYYC VRSIYYYGSS PFDFWGQGTT LTVSSGGGSG GGSGGGGSDI VMTQATSSVP VTPGESVSIS C RSSKSLLH SNGNTYLYWF LQRPGQSPQL LIYRMSNLAS GVPDRFSGSG SGTAFTLTIS RLEAEDVGVY YCMQHLEYPL TF GAGTKLE LKAAAGNSLV PRGSHHHHHH HH |
-Experimental details
-Structure determination
| Method | cryo EM |
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Processing | single particle reconstruction |
| Aggregation state | particle |
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Sample preparation
| Buffer | pH: 7.5 |
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| Vitrification | Cryogen name: ETHANE |
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Electron microscopy
| Microscope | TFS KRIOS |
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| Image recording | Film or detector model: FEI FALCON IV (4k x 4k) / Average electron dose: 40.0 e/Å2 |
| Electron beam | Acceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN |
| Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: OTHER / Nominal defocus max: 1.5 µm / Nominal defocus min: 0.5 µm |
| Experimental equipment | ![]() Model: Titan Krios / Image courtesy: FEI Company |
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Keywords
Homo sapiens (human)
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Processing
FIELD EMISSION GUN
