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Open data
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Basic information
Entry | Database: PDB / ID: 6lfm | ||||||
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Title | Cryo-EM structure of a class A GPCR | ||||||
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![]() | MEMBRANE PROTEIN / G protein coupled-receptor | ||||||
Function / homology | ![]() interleukin-8-mediated signaling pathway / interleukin-8 receptor activity / mast cell granule / regulation of single stranded viral RNA replication via double stranded DNA intermediate / regulation of entry of bacterium into host cell / interleukin-8 receptor binding / interleukin-8 binding / positive regulation of cellular biosynthetic process / C-X-C chemokine receptor activity / negative regulation of cell adhesion molecule production ...interleukin-8-mediated signaling pathway / interleukin-8 receptor activity / mast cell granule / regulation of single stranded viral RNA replication via double stranded DNA intermediate / regulation of entry of bacterium into host cell / interleukin-8 receptor binding / interleukin-8 binding / positive regulation of cellular biosynthetic process / C-X-C chemokine receptor activity / negative regulation of cell adhesion molecule production / negative regulation of G protein-coupled receptor signaling pathway / ATF4 activates genes in response to endoplasmic reticulum stress / CXCR chemokine receptor binding / embryonic digestive tract development / induction of positive chemotaxis / C-C chemokine receptor activity / C-C chemokine binding / neutrophil activation / cellular response to fibroblast growth factor stimulus / chemokine-mediated signaling pathway / positive regulation of neutrophil chemotaxis / Chemokine receptors bind chemokines / chemokine activity / dendritic cell chemotaxis / Interleukin-10 signaling / Adenylate cyclase inhibitory pathway / positive regulation of protein localization to cell cortex / cellular response to interleukin-1 / regulation of cAMP-mediated signaling / cellular defense response / regulation of cell adhesion / D2 dopamine receptor binding / G protein-coupled serotonin receptor binding / regulation of mitotic spindle organization / cellular response to forskolin / adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway / response to endoplasmic reticulum stress / Peptide ligand-binding receptors / neutrophil chemotaxis / secretory granule membrane / Regulation of insulin secretion / G protein-coupled receptor binding / G protein-coupled receptor activity / calcium-mediated signaling / G-protein beta/gamma-subunit complex binding / Olfactory Signaling Pathway / Activation of the phototransduction cascade / adenylate cyclase-modulating G protein-coupled receptor signaling pathway / response to molecule of bacterial origin / 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 / Activation of G protein gated Potassium channels / Inhibition of voltage gated Ca2+ channels via Gbeta/gamma subunits / receptor internalization / Prostacyclin signalling through prostacyclin receptor / Glucagon signaling in metabolic regulation / G beta:gamma signalling through CDC42 / mitotic spindle / 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 / response to peptide hormone / photoreceptor disc membrane / Adrenaline,noradrenaline inhibits insulin secretion / Glucagon-type ligand receptors / 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 / Cooperation of PDCL (PhLP1) and TRiC/CCT in G-protein beta folding / antimicrobial humoral immune response mediated by antimicrobial peptide / 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 / microtubule cytoskeleton / G alpha (12/13) signalling events / extracellular vesicle / signaling receptor complex adaptor activity / Thrombin signalling through proteinase activated receptors (PARs) / GTPase binding / retina development in camera-type eye / phospholipase C-activating G protein-coupled receptor signaling pathway / Ca2+ pathway / cellular response to tumor necrosis factor / heparin binding / cell cortex Similarity search - Function | ||||||
Biological species | ![]() | ||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.5 Å | ||||||
![]() | Liu, Z.J. / Hua, T. / Liu, K.W. / Wu, L.J. | ||||||
![]() | ![]() Title: Structural basis of CXC chemokine receptor 2 activation and signalling. Authors: Kaiwen Liu / Lijie Wu / Shuguang Yuan / Meng Wu / Yueming Xu / Qianqian Sun / Shu Li / Suwen Zhao / Tian Hua / Zhi-Jie Liu / ![]() Abstract: Chemokines and their receptors mediate cell migration, which influences multiple fundamental biological processes and disease conditions such as inflammation and cancer. Although ample effort has ...Chemokines and their receptors mediate cell migration, which influences multiple fundamental biological processes and disease conditions such as inflammation and cancer. Although ample effort has been invested into the structural investigation of the chemokine receptors and receptor-chemokine recognition, less is known about endogenous chemokine-induced receptor activation and G-protein coupling. Here we present the cryo-electron microscopy structures of interleukin-8 (IL-8, also known as CXCL8)-activated human CXC chemokine receptor 2 (CXCR2) in complex with G protein, along with a crystal structure of CXCR2 bound to a designed allosteric antagonist. Our results reveal a unique shallow mode of binding between CXCL8 and CXCR2, and also show the interactions between CXCR2 and G protein. Further structural analysis of the inactive and active states of CXCR2 reveals a distinct activation process and the competitive small-molecule antagonism of chemokine receptors. In addition, our results provide insights into how a G-protein-coupled receptor is activated by an endogenous protein molecule, which will assist in the rational development of therapeutics that target the chemokine system for better pharmacological profiles. | ||||||
History |
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Structure visualization
Movie |
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Structure viewer | Molecule: ![]() ![]() |
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Downloads & links
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Download
PDBx/mmCIF format | ![]() | 253.5 KB | Display | ![]() |
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PDB format | ![]() | 204.5 KB | Display | ![]() |
PDBx/mmJSON format | ![]() | Tree view | ![]() | |
Others | ![]() |
-Validation report
Summary document | ![]() | 930.8 KB | Display | ![]() |
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Full document | ![]() | 943.9 KB | Display | |
Data in XML | ![]() | 40.3 KB | Display | |
Data in CIF | ![]() | 61.9 KB | Display | |
Arichive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 0877MC ![]() 0879C ![]() 6lflC ![]() 6lfoC M: map data used to model this data C: citing same article ( |
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Similar structure data |
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Links
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Assembly
Deposited unit | ![]()
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Components
-Guanine nucleotide-binding protein ... , 3 types, 3 molecules ABC
#1: Protein | Mass: 40283.836 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() |
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#2: Protein | Mass: 38045.629 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() |
#3: Protein | Mass: 7861.143 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() |
-Protein , 2 types, 3 molecules DER
#4: Protein | Mass: 8401.807 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() #5: Protein | | Mass: 40798.121 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() |
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-Antibody / Non-polymers , 2 types, 2 molecules S![](data/chem/img/CLR.gif)
![](data/chem/img/CLR.gif)
#6: Antibody | Mass: 27784.896 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() |
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#7: Chemical | ChemComp-CLR / |
-Details
Has ligand of interest | Y |
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-Experimental details
-Experiment
Experiment | Method: ELECTRON MICROSCOPY |
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EM experiment | Aggregation state: PARTICLE / 3D reconstruction method: single particle reconstruction |
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Sample preparation
Component | Name: Ternary complex of chemokine, GPCR and G protein / Type: COMPLEX / Entity ID: #1-#6 / Source: RECOMBINANT |
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Molecular weight | Value: 0.15 MDa / Experimental value: YES |
Source (natural) | Organism: ![]() |
Source (recombinant) | Organism: ![]() ![]() |
Buffer solution | pH: 7.5 |
Specimen | Conc.: 1 mg/ml / Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES |
Specimen support | Grid material: GOLD / Grid mesh size: 300 divisions/in. / Grid type: Homemade |
Vitrification | Instrument: FEI VITROBOT MARK IV / Cryogen name: ETHANE / Humidity: 100 % / Chamber temperature: 277 K |
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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: ![]() |
Electron lens | Mode: BRIGHT FIELD / Nominal magnification: 130000 X / Calibrated magnification: 130000 X / Nominal defocus max: 2000 nm / Nominal defocus min: 800 nm / Calibrated defocus min: 800 nm / Calibrated defocus max: 2000 nm / Cs: 2.7 mm / C2 aperture diameter: 50 µm / Alignment procedure: BASIC |
Specimen holder | Cryogen: NITROGEN / Specimen holder model: FEI TITAN KRIOS AUTOGRID HOLDER |
Image recording | Average exposure time: 0.8 sec. / Electron dose: 8 e/Å2 / Detector mode: SUPER-RESOLUTION / Film or detector model: GATAN K2 SUMMIT (4k x 4k) / Num. of grids imaged: 5 / Num. of real images: 15688 |
EM imaging optics | Energyfilter slit width: 20 eV |
Image scans | Width: 7420 / Height: 7676 / Movie frames/image: 45 |
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Processing
EM software |
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CTF correction | Details: Patch CTF refinement / Type: PHASE FLIPPING AND AMPLITUDE CORRECTION | ||||||||||||||||||||||||||||
Symmetry | Point symmetry: C1 (asymmetric) | ||||||||||||||||||||||||||||
3D reconstruction | Resolution: 3.5 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 207972 / Algorithm: SIMULTANEOUS ITERATIVE (SIRT) / Num. of class averages: 1 / Symmetry type: POINT | ||||||||||||||||||||||||||||
Atomic model building | B value: 93.7 / Protocol: AB INITIO MODEL / Space: REAL / Target criteria: Correlation coefficient | ||||||||||||||||||||||||||||
Atomic model building | PDB-ID: 6N4B |