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- EMDB-33107: Cryo-EM structure of the human chemokine receptor CX3CR1 in compl... -
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Open data
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Basic information
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Title | Cryo-EM structure of the human chemokine receptor CX3CR1 in complex with Gi1 | ||||||||||||
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Function / homology | ![]() C-X3-C chemokine receptor activity / dendritic tree / multiple spine synapse organization, single dendrite / negative regulation of microglial cell mediated cytotoxicity / C-X3-C chemokine binding / regulation of microglial cell migration / CX3C chemokine receptor binding / negative regulation of hippocampal neuron apoptotic process / microglial cell activation involved in immune response / host-mediated regulation of intestinal microbiota composition ...C-X3-C chemokine receptor activity / dendritic tree / multiple spine synapse organization, single dendrite / negative regulation of microglial cell mediated cytotoxicity / C-X3-C chemokine binding / regulation of microglial cell migration / CX3C chemokine receptor binding / negative regulation of hippocampal neuron apoptotic process / microglial cell activation involved in immune response / host-mediated regulation of intestinal microbiota composition / autocrine signaling / synapse pruning / central nervous system maturation / positive regulation of microglial cell migration / synapse maturation / antifungal innate immune response / chemokine receptor activity / positive regulation of I-kappaB phosphorylation / C-C chemokine receptor activity / C-C chemokine binding / leukocyte tethering or rolling / regulation of tumor necrosis factor production / G protein-coupled peptide receptor activity / positive regulation of monocyte chemotaxis / leukocyte chemotaxis / regulation of nitric oxide biosynthetic process / Chemokine receptors bind chemokines / negative regulation of interleukin-1 beta production / positive regulation of neurogenesis / positive regulation of neuroblast proliferation / neuronal cell body membrane / plasma membrane => GO:0005886 / social behavior / negative regulation of apoptotic signaling pathway / negative regulation of long-term synaptic potentiation / regulation of neurogenesis / Adenylate cyclase inhibitory pathway / positive regulation of protein localization to cell cortex / regulation of cAMP-mediated signaling / cellular defense response / D2 dopamine receptor binding / G protein-coupled serotonin receptor binding / regulation of mitotic spindle organization / cellular response to forskolin / cellular response to transforming growth factor beta stimulus / adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway / cell chemotaxis / negative regulation of cell migration / response to ischemia / Regulation of insulin secretion / G protein-coupled receptor binding / G protein-coupled receptor activity / calcium-mediated signaling / G-protein beta/gamma-subunit complex binding / modulation of chemical synaptic transmission / Olfactory Signaling Pathway / brain development / Activation of the phototransduction cascade / adenylate cyclase-modulating G protein-coupled receptor signaling pathway / regulation of synaptic plasticity / 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 / memory / response to peptide hormone / ADP signalling through P2Y purinoceptor 12 / G beta:gamma signalling through BTK / Synthesis, secretion, and inactivation of Glucagon-like Peptide-1 (GLP-1) / Sensory perception of sweet, bitter, and umami (glutamate) taste / photoreceptor disc membrane / Adrenaline,noradrenaline inhibits insulin secretion / Glucagon-type ligand receptors / response to wounding / Vasopressin regulates renal water homeostasis via Aquaporins / G alpha (z) signalling events / cellular response to catecholamine stimulus / Glucagon-like Peptide-1 (GLP1) regulates insulin secretion / ADORA2B mediated anti-inflammatory cytokines production / sensory perception of taste / ADP signalling through P2Y purinoceptor 1 / adenylate cyclase-activating dopamine receptor signaling pathway / G beta:gamma signalling through PI3Kgamma / cellular response to prostaglandin E stimulus / positive regulation of angiogenesis / Cooperation of PDCL (PhLP1) and TRiC/CCT in G-protein beta folding / GPER1 signaling / GDP binding / chemotaxis / G-protein beta-subunit binding / Inactivation, recovery and regulation of the phototransduction cascade / heterotrimeric G-protein complex / G alpha (12/13) signalling events / extracellular vesicle Similarity search - Function | ||||||||||||
Biological species | ![]() | ||||||||||||
Method | single particle reconstruction / cryo EM / Resolution: 2.8 Å | ||||||||||||
![]() | Lu M / Zhao W / Han S / Zhu Y / Wu B / Zhao Q | ||||||||||||
Funding support | ![]()
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![]() | ![]() Title: Activation of the human chemokine receptor CX3CR1 regulated by cholesterol. Authors: Minmin Lu / Wenli Zhao / Shuo Han / Xiaowen Lin / Tingyu Xu / Qiuxiang Tan / Mu Wang / Cuiying Yi / Xiaojing Chu / Weibo Yang / Ya Zhu / Beili Wu / Qiang Zhao / ![]() Abstract: As the only member of the CX3C chemokine receptor subfamily, CX3CR1 binds to its sole endogenous ligand CX3CL1, which shows notable potential as a therapeutic target in atherosclerosis, cancer, and ...As the only member of the CX3C chemokine receptor subfamily, CX3CR1 binds to its sole endogenous ligand CX3CL1, which shows notable potential as a therapeutic target in atherosclerosis, cancer, and neuropathy. However, the drug development of CX3CR1 is hampered partially by the lack of structural information. Here, we present two cryo-electron microscopy structures of CX3CR1-G complexes in ligand-free and CX3CL1-bound states at 2.8- and 3.4-Å resolution, respectively. Together with functional data, the structures reveal the key factors that govern the recognition of CX3CL1 by both CX3CR1 and US28. A much smaller conformational change of helix VI upon activation than previously solved class A GPCR-G complex structures is observed in CX3CR1, which may correlate with three cholesterol molecules that play essential roles in conformation stabilization and signaling transduction. Thus, our data deepen the understanding of cholesterol modulation in GPCR (G protein-coupled receptor) signaling and provide insights into the diversity of G protein coupling. | ||||||||||||
History |
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Structure visualization
Supplemental images |
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Downloads & links
-EMDB archive
Map data | ![]() | 59.8 MB | ![]() | |
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Header (meta data) | ![]() ![]() | 18.6 KB 18.6 KB | Display Display | ![]() |
Images | ![]() | 126.5 KB | ||
Others | ![]() ![]() | 49.6 MB 49.6 MB | ||
Archive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 7xbwMC ![]() 7xbxC 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: 1.045 Å | ||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||
Details | EMDB XML:
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-Supplemental data
-Half map: #1
File | emd_33107_half_map_1.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Half map: #2
File | emd_33107_half_map_2.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
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Sample components
-Entire : Chemokine receptor CX3CR1 in complex with Gi1
Entire | Name: Chemokine receptor CX3CR1 in complex with Gi1 |
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Components |
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-Supramolecule #1: Chemokine receptor CX3CR1 in complex with Gi1
Supramolecule | Name: Chemokine receptor CX3CR1 in complex with Gi1 / type: complex / Chimera: Yes / ID: 1 / Parent: 0 / Macromolecule list: #1-#4 |
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Source (natural) | Organism: ![]() |
Recombinant expression | Organism: ![]() ![]() |
-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: ![]() |
Molecular weight | Theoretical: 40.447141 KDa |
Recombinant expression | Organism: ![]() ![]() |
Sequence | String: MGCTLSAEDK AAVERSKMID RNLREDGEKA AREVKLLLLG AGESGKCTIV KQMKIIHEAG YSEEECKQYK AVVYSNTIQS IIAIIRAMG RLKIDFGDSA RADDARQLFV LAGAAEEGFM TAELAGVIKR LWKDSGVQAC FNRSREYQLN DSAAYYLNDL D RIAQPNYI ...String: MGCTLSAEDK AAVERSKMID RNLREDGEKA AREVKLLLLG AGESGKCTIV KQMKIIHEAG YSEEECKQYK AVVYSNTIQS IIAIIRAMG RLKIDFGDSA RADDARQLFV LAGAAEEGFM TAELAGVIKR LWKDSGVQAC FNRSREYQLN DSAAYYLNDL D RIAQPNYI PTQQDVLRTR VKTTGIVETH FTFKDLHFKM FDVTAQRSER KKWIHCFEGV TAIIFCVALS DYDLVLAEDE EM NRMHASM KLFDSICNNK WFTDTSIILF LNKKDLFEEK IKKSPLTICY PEYAGSNTYE EAAAYIQCQF EDLNKRKDTK EIY THFTCS TDTKNVQFVF DAVTDVIIKN NLKDCGLF |
-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: ![]() |
Molecular weight | Theoretical: 38.245805 KDa |
Recombinant expression | Organism: ![]() ![]() |
Sequence | String: HHHHHHMSEL DQLRQEAEQL KNQIRDARKA CADATLSQIT NNIDPVGRIQ MRTRRTLRGH LAKIYAMHWG TDSRLLVSAS QDGKLIIWD SYTTNKVHAI PLRSSWVMTC AYAPSGNYVA CGGLDNICSI YNLKTREGNV RVSRELAGHT GYLSCCRFLD D NQIVTSSG ...String: HHHHHHMSEL DQLRQEAEQL KNQIRDARKA CADATLSQIT NNIDPVGRIQ MRTRRTLRGH LAKIYAMHWG TDSRLLVSAS QDGKLIIWD SYTTNKVHAI PLRSSWVMTC AYAPSGNYVA CGGLDNICSI YNLKTREGNV RVSRELAGHT GYLSCCRFLD D NQIVTSSG DTTCALWDIE TGQQTTTFTG HTGDVMSLSL APDTRLFVSG ACDASAKLWD VREGMCRQTF TGHESDINAI CF FPNGNAF ATGSDDATCR LFDLRADQEL MTYSHDNIIC GITSVSFSKS GRLLLAGYDD FNCNVWDALK ADRAGVLAGH DNR VSCLGV TDDGMAVATG SWDSFLKIWN |
-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: ![]() |
Molecular weight | Theoretical: 7.861143 KDa |
Recombinant expression | Organism: ![]() ![]() |
Sequence | String: MASNNTASIA QARKLVEQLK MEANIDRIKV SKAAADLMAY CEAHAKEDPL LTPVPASENP FREKKFFCAI L |
-Macromolecule #4: CX3C chemokine receptor 1
Macromolecule | Name: CX3C chemokine receptor 1 / type: protein_or_peptide / ID: 4 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() |
Molecular weight | Theoretical: 41.07268 KDa |
Recombinant expression | Organism: ![]() ![]() |
Sequence | String: MDQFPESVTE NFEYDDLAEA CYIGDIVVFG TVFLSIFYSV IFAIGLVGNL LVVFALTNSK KPKSVTDIYL LNLALSDLLF VATLPFWTH YLINEKGLHN AMCKFTTAFF FIGFFGSIFF LTVISIDRYL AIVLAANSMN NRTVQHGVTI SLGVWAAAIL V AAPQFMFT ...String: MDQFPESVTE NFEYDDLAEA CYIGDIVVFG TVFLSIFYSV IFAIGLVGNL LVVFALTNSK KPKSVTDIYL LNLALSDLLF VATLPFWTH YLINEKGLHN AMCKFTTAFF FIGFFGSIFF LTVISIDRYL AIVLAANSMN NRTVQHGVTI SLGVWAAAIL V AAPQFMFT KQKENECLGD YPEVLQEIWP VLRNVETNFL GFLLPLLIMS YCYFRIIQTL FSSKNHKKAK AIKLILLVVI VF FLFWTPY NVVIFLETLK LYDFFPSCDM RKDLRLALSV TETVAFSHCC LNPLIYAFAG EKFRRYLYHL YGKCLAVLEF LEV LFQGPW SHPQFEKGGG SGGGSGGSAW SHPQFEKDYK DDDDK |
-Macromolecule #5: CHOLESTEROL
Macromolecule | Name: CHOLESTEROL / type: ligand / ID: 5 / Number of copies: 3 / 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
Buffer | pH: 7.5 |
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Vitrification | Cryogen name: ETHANE |
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Electron microscopy
Microscope | FEI TITAN KRIOS |
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Image recording | Film or detector model: GATAN K3 BIOQUANTUM (6k x 4k) / Average electron dose: 2.1875 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: ![]() |
Electron optics | Illumination mode: SPOT SCAN / Imaging mode: BRIGHT FIELD / Nominal defocus max: 1.5 µm / Nominal defocus min: 0.8 µm |
Experimental equipment | ![]() Model: Titan Krios / Image courtesy: FEI Company |
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Image processing
Final reconstruction | Resolution.type: BY AUTHOR / Resolution: 2.8 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 702722 |
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Initial angle assignment | Type: MAXIMUM LIKELIHOOD |
Final angle assignment | Type: MAXIMUM LIKELIHOOD |