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Yorodumi- PDB-7xbw: Cryo-EM structure of the human chemokine receptor CX3CR1 in compl... -
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-Basic information
Entry | Database: PDB / ID: 7xbw | ||||||||||||
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Title | Cryo-EM structure of the human chemokine receptor CX3CR1 in complex with Gi1 | ||||||||||||
Components |
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Keywords | SIGNALING PROTEIN / G protein-coupled receptor / chemokine receptor / CX3CR1 | ||||||||||||
Function / homology | Function and homology information C-X3-C chemokine receptor activity / dendritic tree / multiple spine synapse organization, single dendrite / negative regulation of microglial cell mediated cytotoxicity / regulation of microglial cell migration / CX3C chemokine receptor binding / negative regulation of hippocampal neuron apoptotic process / C-X3-C chemokine binding / 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 / regulation of microglial cell migration / CX3C chemokine receptor binding / negative regulation of hippocampal neuron apoptotic process / C-X3-C chemokine binding / 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 / leukocyte tethering or rolling / C-C chemokine receptor activity / C-C chemokine binding / 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 / negative regulation of cell migration / cell chemotaxis / Regulation of insulin secretion / response to ischemia / 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 / regulation of synaptic plasticity / Olfactory Signaling Pathway / Activation of the phototransduction cascade / adenylate cyclase-modulating 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 activation / G protein-coupled acetylcholine receptor signaling pathway / brain development / 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 / ADP signalling through P2Y purinoceptor 12 / G beta:gamma signalling through BTK / response to peptide hormone / 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 / Vasopressin regulates renal water homeostasis via Aquaporins / response to wounding / 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 / Cooperation of PDCL (PhLP1) and TRiC/CCT in G-protein beta folding / positive regulation of angiogenesis / 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 | Homo sapiens (human) | ||||||||||||
Method | ELECTRON MICROSCOPY / 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, 3items
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Citation | Journal: Sci Adv / Year: 2022 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
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 7xbw.cif.gz | 168.5 KB | Display | PDBx/mmCIF format |
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PDB format | pdb7xbw.ent.gz | 126 KB | Display | PDB format |
PDBx/mmJSON format | 7xbw.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 7xbw_validation.pdf.gz | 1.2 MB | Display | wwPDB validaton report |
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Full document | 7xbw_full_validation.pdf.gz | 1.2 MB | Display | |
Data in XML | 7xbw_validation.xml.gz | 35.9 KB | Display | |
Data in CIF | 7xbw_validation.cif.gz | 51.7 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/xb/7xbw ftp://data.pdbj.org/pub/pdb/validation_reports/xb/7xbw | HTTPS FTP |
-Related structure data
Related structure data | 33107MC 7xbxC M: map data used to model this data C: citing same article (ref.) |
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Similar structure data | Similarity search - Function & homologyF&H Search |
-Links
-Assembly
Deposited unit |
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1 |
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-Components
#1: Protein | Mass: 40447.141 Da / Num. of mol.: 1 / Mutation: S47C,G202T,G203A,E245A,A326S Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: GNAI1 / Production host: Spodoptera frugiperda (fall armyworm) / References: UniProt: P63096 | ||
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#2: Protein | Mass: 38245.805 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: GNB1 / Production host: Spodoptera frugiperda (fall armyworm) / References: UniProt: P62873 | ||
#3: Protein | Mass: 7861.143 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: GNG2 / Production host: Spodoptera frugiperda (fall armyworm) / References: UniProt: P59768 | ||
#4: Protein | Mass: 41072.680 Da / Num. of mol.: 1 / Mutation: I120L, C221S, M250V Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: CX3CR1, CMKBRL1, GPR13 / Production host: Spodoptera frugiperda (fall armyworm) / References: UniProt: P49238 | ||
#5: Chemical | Has ligand of interest | N | |
-Experimental details
-Experiment
Experiment | Method: ELECTRON MICROSCOPY |
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EM experiment | Aggregation state: PARTICLE / 3D reconstruction method: single particle reconstruction |
-Sample preparation
Component | Name: Chemokine receptor CX3CR1 in complex with Gi1 / Type: COMPLEX / Entity ID: #1-#4 / Source: RECOMBINANT |
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Source (natural) | Organism: Homo sapiens (human) |
Source (recombinant) | Organism: Spodoptera frugiperda (fall armyworm) |
Buffer solution | pH: 7.5 |
Specimen | Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES |
Vitrification | Cryogen name: ETHANE |
-Electron microscopy imaging
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |
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Microscopy | Model: FEI TITAN KRIOS |
Electron gun | Electron source: FIELD EMISSION GUN / Accelerating voltage: 300 kV / Illumination mode: SPOT SCAN |
Electron lens | Mode: BRIGHT FIELD / Nominal defocus max: 1500 nm / Nominal defocus min: 800 nm |
Image recording | Electron dose: 2.1875 e/Å2 / Film or detector model: GATAN K3 BIOQUANTUM (6k x 4k) |
-Processing
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CTF correction | Type: NONE | ||||||||||||||||||||||||
3D reconstruction | Resolution: 2.8 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 702722 / Symmetry type: POINT | ||||||||||||||||||||||||
Refinement | Cross valid method: NONE Stereochemistry target values: GeoStd + Monomer Library + CDL v1.2 | ||||||||||||||||||||||||
Displacement parameters | Biso mean: 52.17 Å2 | ||||||||||||||||||||||||
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