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Yorodumi- EMDB-33107: Cryo-EM structure of the human chemokine receptor CX3CR1 in compl... -
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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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Keywords | G protein-coupled receptor / chemokine receptor / CX3CR1 / SIGNALING PROTEIN | ||||||||||||
| Function / homology | Function and homology informationC-X3-C chemokine receptor activity / dendritic tree / multiple spine synapse organization, single dendrite / negative regulation of microglial cell mediated cytotoxicity / macropinosome membrane / C-X3-C chemokine binding / regulation of microglial cell migration / CX3C chemokine receptor binding / autocrine signaling / host-mediated modulation 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 / macropinosome membrane / C-X3-C chemokine binding / regulation of microglial cell migration / CX3C chemokine receptor binding / autocrine signaling / host-mediated modulation of intestinal microbiota composition / microglial cell activation involved in immune response / synapse pruning / central nervous system maturation / synapse maturation / negative regulation of hippocampal neuron apoptotic process / antifungal innate immune response / chemokine receptor activity / leukocyte tethering or rolling / regulation of tumor necrosis factor production / C-C chemokine receptor activity / C-C chemokine binding / positive regulation of monocyte chemotaxis / G protein-coupled peptide receptor activity / leukocyte chemotaxis / regulation of nitric oxide biosynthetic process / Chemokine receptors bind chemokines / positive regulation of neurogenesis / negative regulation of interleukin-1 beta production / positive regulation of neuroblast proliferation / RSV-host interactions / neuronal cell body membrane / Respiratory syncytial virus (RSV) attachment and entry / negative regulation of apoptotic signaling pathway / regulation of neurogenesis / cellular defense response / social behavior / adenylate cyclase inhibitor activity / positive regulation of protein localization to cell cortex / T cell migration / positive regulation of relaxation of smooth muscle / Adenylate cyclase inhibitory pathway / D2 dopamine receptor binding / adenylate cyclase-inhibiting serotonin receptor signaling pathway / G protein-coupled serotonin receptor binding / cellular response to forskolin / negative regulation of angiogenesis / response to ischemia / regulation of mitotic spindle organization / chemokine-mediated signaling pathway / cell chemotaxis / Regulation of insulin secretion / neuropeptide signaling pathway / calcium-mediated signaling / response to prostaglandin E / positive regulation of cholesterol biosynthetic process / brain development / negative regulation of insulin secretion / regulation of synaptic plasticity / G protein-coupled receptor binding / response to wounding / response to peptide hormone / G protein-coupled receptor activity / modulation of chemical synaptic transmission / adenylate cyclase-modulating G protein-coupled receptor signaling pathway / G-protein beta/gamma-subunit complex binding / centriolar satellite / chemotaxis / adenylate cyclase-inhibiting 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 / G beta:gamma signalling through BTK / Synthesis, secretion, and inactivation of Glucagon-like Peptide-1 (GLP-1) / photoreceptor disc membrane / ADP signalling through P2Y purinoceptor 12 / Sensory perception of sweet, bitter, and umami (glutamate) taste / GDP binding / Glucagon-type ligand receptors / Adrenaline,noradrenaline inhibits insulin secretion / 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 / cell-cell signaling / ADP signalling through P2Y purinoceptor 1 / ADORA2B mediated anti-inflammatory cytokines production / 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 / GPER1 signaling / cellular response to prostaglandin E stimulus Similarity search - Function | ||||||||||||
| Biological species | Homo sapiens (human) | ||||||||||||
| Method | single particle reconstruction / cryo EM / Resolution: 2.8 Å | ||||||||||||
Authors | Lu M / Zhao W / Han S / Zhu Y / Wu B / Zhao Q | ||||||||||||
| Funding support | China, 3 items
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Citation | Journal: Sci Adv / Year: 2022Title: 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. | ||||||||||||
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Structure visualization
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Downloads & links
-EMDB archive
| Map data | emd_33107.map.gz | 59.8 MB | EMDB map data format | |
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| Header (meta data) | emd-33107-v30.xml emd-33107.xml | 18.5 KB 18.5 KB | Display Display | EMDB header |
| Images | emd_33107.png | 126.5 KB | ||
| Filedesc metadata | emd-33107.cif.gz | 6.1 KB | ||
| Others | emd_33107_half_map_1.map.gz emd_33107_half_map_2.map.gz | 49.6 MB 49.6 MB | ||
| Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-33107 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-33107 | 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 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_33107.map.gz / Format: CCP4 / Size: 64 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||
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| Projections & slices | Image control
Images are generated by Spider. | ||||||||||||||||||||||||||||||||||||
| 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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-Half map: #2
| File | emd_33107_half_map_2.map | ||||||||||||
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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 / ID: 1 / Parent: 0 / Macromolecule list: #1-#4 |
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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: 40.447141 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 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: 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 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: ![]() |
| 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: 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: Homo sapiens (human) |
| 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 UniProtKB: CX3C chemokine receptor 1 |
-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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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 | 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: FIELD EMISSION GUN |
| 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
| Startup model | Type of model: INSILICO MODEL |
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| Final reconstruction | Resolution.type: BY AUTHOR / Resolution: 2.8 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 702722 |
| Initial angle assignment | Type: MAXIMUM LIKELIHOOD |
| Final angle assignment | Type: MAXIMUM LIKELIHOOD |
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Keywords
Homo sapiens (human)
Authors
China, 3 items
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Y (Row.)
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FIELD EMISSION GUN
