+Open data
-Basic information
Entry | Database: PDB / ID: 8sg1 | ||||||
---|---|---|---|---|---|---|---|
Title | Cryo-EM structure of CMKLR1 signaling complex | ||||||
Components |
| ||||||
Keywords | SIGNALING PROTEIN / GPCR / Peptide agonist / Chemerin9 / Membrane protein | ||||||
Function / homology | Function and homology information adipokinetic hormone binding / adipokinetic hormone receptor activity / complement receptor activity / chemokine receptor activity / Class A/1 (Rhodopsin-like receptors) / complement receptor mediated signaling pathway / negative regulation of interleukin-12 production / positive regulation of macrophage chemotaxis / negative regulation of NF-kappaB transcription factor activity / Adenylate cyclase inhibitory pathway ...adipokinetic hormone binding / adipokinetic hormone receptor activity / complement receptor activity / chemokine receptor activity / Class A/1 (Rhodopsin-like receptors) / complement receptor mediated signaling pathway / negative regulation of interleukin-12 production / positive regulation of macrophage chemotaxis / negative regulation of NF-kappaB transcription factor activity / Adenylate cyclase inhibitory pathway / positive regulation of protein localization to cell cortex / regulation of cAMP-mediated signaling / positive regulation of fat cell differentiation / D2 dopamine receptor binding / G protein-coupled serotonin receptor binding / regulation of mitotic spindle organization / cellular response to forskolin / regulation of calcium-mediated signaling / adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway / Regulation of insulin secretion / skeletal system development / G protein-coupled receptor binding / G protein-coupled receptor activity / G-protein beta/gamma-subunit complex binding / Olfactory Signaling Pathway / Activation of the phototransduction cascade / G beta:gamma signalling through PLC beta / Presynaptic function of Kainate receptors / Thromboxane signalling through TP receptor / adenylate cyclase-modulating G protein-coupled receptor signaling pathway / 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 / Prostacyclin signalling through prostacyclin receptor / Glucagon signaling in metabolic regulation / G beta:gamma signalling through CDC42 / ADP signalling through P2Y purinoceptor 12 / G beta:gamma signalling through BTK / Sensory perception of sweet, bitter, and umami (glutamate) taste / response to peptide hormone / Synthesis, secretion, and inactivation of Glucagon-like Peptide-1 (GLP-1) / 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 / adenylate cyclase-activating dopamine receptor signaling pathway / ADP signalling through P2Y purinoceptor 1 / G beta:gamma signalling through PI3Kgamma / cellular response to prostaglandin E stimulus / Cooperation of PDCL (PhLP1) and TRiC/CCT in G-protein beta folding / sensory perception of taste / GPER1 signaling / GDP binding / G-protein beta-subunit binding / heterotrimeric G-protein complex / Inactivation, recovery and regulation of the phototransduction cascade / extracellular vesicle / G alpha (12/13) signalling events / chemotaxis / signaling receptor complex adaptor activity / Thrombin signalling through proteinase activated receptors (PARs) / retina development in camera-type eye / signaling receptor activity / GTPase binding / Ca2+ pathway / phospholipase C-activating G protein-coupled receptor signaling pathway / positive regulation of cold-induced thermogenesis / cell cortex / midbody / positive regulation of cytosolic calcium ion concentration / G alpha (i) signalling events / fibroblast proliferation / G alpha (s) signalling events / G alpha (q) signalling events / Ras protein signal transduction / cell population proliferation / Extra-nuclear estrogen signaling / immune response / cell cycle / inflammatory response / G protein-coupled receptor signaling pathway / cell division / lysosomal membrane / GTPase activity / centrosome / synapse / protein-containing complex binding / GTP binding / nucleolus / magnesium ion binding / signal transduction / extracellular exosome / nucleoplasm / membrane / plasma membrane Similarity search - Function | ||||||
Biological species | Homo sapiens (human) Mus musculus (house mouse) | ||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 2.94 Å | ||||||
Authors | Zhang, X. / Zhang, C. | ||||||
Funding support | United States, 1items
| ||||||
Citation | Journal: PLoS Biol / Year: 2023 Title: Structural basis of G protein-Coupled receptor CMKLR1 activation and signaling induced by a chemerin-derived agonist. Authors: Xuan Zhang / Tina Weiß / Mary Hongying Cheng / Siqi Chen / Carla Katharina Ambrosius / Anne Sophie Czerniak / Kunpeng Li / Mingye Feng / Ivet Bahar / Annette G Beck-Sickinger / Cheng Zhang / Abstract: Chemokine-like receptor 1 (CMKLR1), also known as chemerin receptor 23 (ChemR23) or chemerin receptor 1, is a chemoattractant G protein-coupled receptor (GPCR) that responds to the adipokine chemerin ...Chemokine-like receptor 1 (CMKLR1), also known as chemerin receptor 23 (ChemR23) or chemerin receptor 1, is a chemoattractant G protein-coupled receptor (GPCR) that responds to the adipokine chemerin and is highly expressed in innate immune cells, including macrophages and neutrophils. The signaling pathways of CMKLR1 can lead to both pro- and anti-inflammatory effects depending on the ligands and physiological contexts. To understand the molecular mechanisms of CMKLR1 signaling, we determined a high-resolution cryo-electron microscopy (cryo-EM) structure of the CMKLR1-Gi signaling complex with chemerin9, a nanopeptide agonist derived from chemerin, which induced complex phenotypic changes of macrophages in our assays. The cryo-EM structure, together with molecular dynamics simulations and mutagenesis studies, revealed the molecular basis of CMKLR1 signaling by elucidating the interactions at the ligand-binding pocket and the agonist-induced conformational changes. Our results are expected to facilitate the development of small molecule CMKLR1 agonists that mimic the action of chemerin9 to promote the resolution of inflammation. | ||||||
History |
|
-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
---|
-Downloads & links
-Download
PDBx/mmCIF format | 8sg1.cif.gz | 237.1 KB | Display | PDBx/mmCIF format |
---|---|---|---|---|
PDB format | pdb8sg1.ent.gz | 183 KB | Display | PDB format |
PDBx/mmJSON format | 8sg1.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/sg/8sg1 ftp://data.pdbj.org/pub/pdb/validation_reports/sg/8sg1 | HTTPS FTP |
---|
-Related structure data
Related structure data | 40450MC M: map data used to model this data C: citing same article (ref.) |
---|---|
Similar structure data | Similarity search - Function & homologyF&H Search |
-Links
-Assembly
Deposited unit |
|
---|---|
1 |
|
-Components
-Guanine nucleotide-binding protein ... , 3 types, 3 molecules BGA
#2: Protein | Mass: 36956.383 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: 6000.000 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: 40122.660 Da / Num. of mol.: 1 / Mutation: S47N, 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 |
-Protein / Protein/peptide / Antibody , 3 types, 3 molecules RLE
#1: Protein | Mass: 33079.715 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: CMKLR1 / Production host: Spodoptera frugiperda (fall armyworm) / References: UniProt: Q99788 |
---|---|
#5: Protein/peptide | Mass: 1063.161 Da / Num. of mol.: 1 / Source method: obtained synthetically / Source: (synth.) Homo sapiens (human) |
#6: Antibody | Mass: 28634.797 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Mus musculus (house mouse) / Production host: Spodoptera frugiperda (fall armyworm) |
-Non-polymers , 2 types, 3 molecules
#7: Chemical | ChemComp-CLR / |
---|---|
#8: Chemical |
-Details
Has ligand of interest | Y |
---|
-Experimental details
-Experiment
Experiment | Method: ELECTRON MICROSCOPY |
---|---|
EM experiment | Aggregation state: PARTICLE / 3D reconstruction method: single particle reconstruction |
-Sample preparation
Component | Name: Chemerin9-CMKLR1-Gi complex / Type: COMPLEX / Entity ID: #1-#6 / Source: MULTIPLE SOURCES |
---|---|
Molecular weight | Experimental value: NO |
Source (natural) | Organism: Spodoptera frugiperda (fall armyworm) |
Source (recombinant) | Organism: Baculovirus expression vector pFastBac1-HM |
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 |
---|---|
Microscopy | Model: FEI TITAN KRIOS |
Electron gun | Electron source: FIELD EMISSION GUN / Accelerating voltage: 300 kV / Illumination mode: FLOOD BEAM |
Electron lens | Mode: BRIGHT FIELDBright-field microscopy / Nominal defocus max: 1800 nm / Nominal defocus min: 1000 nm |
Image recording | Electron dose: 56 e/Å2 / Film or detector model: GATAN K3 BIOQUANTUM (6k x 4k) |
-Processing
CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION |
---|---|
3D reconstruction | Resolution: 2.94 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 242745 / Symmetry type: POINT |