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Yorodumi- PDB-7xk2: Cryo-EM Structure of Human Niacin Receptor HCA2-Gi protein complex -
+Open data
-Basic information
Entry | Database: PDB / ID: 7xk2 | ||||||||||||||||||
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Title | Cryo-EM Structure of Human Niacin Receptor HCA2-Gi protein complex | ||||||||||||||||||
Components |
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Keywords | MEMBRANE PROTEIN / Niacin receptor / hydroxycarboxylic acid receptor 2 / HCA2 / Gi complex | ||||||||||||||||||
Function / homology | Function and homology information nicotinic acid receptor activity / Hydroxycarboxylic acid-binding receptors / neutrophil apoptotic process / positive regulation of neutrophil apoptotic process / Class A/1 (Rhodopsin-like receptors) / positive regulation of adiponectin secretion / Adenylate cyclase inhibitory pathway / positive regulation of protein localization to cell cortex / regulation of cAMP-mediated signaling / negative regulation of lipid catabolic process ...nicotinic acid receptor activity / Hydroxycarboxylic acid-binding receptors / neutrophil apoptotic process / positive regulation of neutrophil apoptotic process / Class A/1 (Rhodopsin-like receptors) / positive regulation of adiponectin secretion / Adenylate cyclase inhibitory pathway / positive regulation of protein localization to cell cortex / regulation of cAMP-mediated signaling / negative regulation of lipid catabolic process / 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 / Regulation of insulin secretion / G protein-coupled receptor binding / G-protein beta/gamma-subunit complex binding / 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 / 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 / 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 / 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 / GPER1 signaling / GDP binding / 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 / signaling receptor complex adaptor activity / Thrombin signalling through proteinase activated receptors (PARs) / cell junction / GTPase binding / retina development in camera-type eye / phospholipase C-activating G protein-coupled receptor signaling pathway / Ca2+ pathway / cell cortex / midbody / G alpha (i) signalling events / fibroblast proliferation / G alpha (s) signalling events / G alpha (q) signalling events / cell population proliferation / Ras protein signal transduction / Extra-nuclear estrogen signaling / cell cycle / G protein-coupled receptor signaling pathway / cell division / lysosomal membrane / GTPase activity / centrosome / synapse / protein-containing complex binding / nucleolus / GTP binding / magnesium ion binding / signal transduction / extracellular exosome / nucleoplasm / membrane / plasma membrane / cytoplasm / cytosol Similarity search - Function | ||||||||||||||||||
Biological species | Homo sapiens (human) | ||||||||||||||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.1 Å | ||||||||||||||||||
Authors | Yang, Y. / Kang, H.J. / Gao, R.G. / Wang, J.J. / Han, G.W. / DiBerto, J.F. / Wu, L.J. / Tong, J.H. / Qu, L. / Wu, Y.R. ...Yang, Y. / Kang, H.J. / Gao, R.G. / Wang, J.J. / Han, G.W. / DiBerto, J.F. / Wu, L.J. / Tong, J.H. / Qu, L. / Wu, Y.R. / Pileski, R. / Li, X.M. / Zhang, X.C. / Zhao, S.W. / Kenakin, T. / Wang, Q. / Stevens, R.C. / Peng, W. / Roth, B.L. / Rao, Z.H. / Liu, Z.J. | ||||||||||||||||||
Funding support | China, 5items
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Citation | Journal: Nat Commun / Year: 2023 Title: Structural insights into the human niacin receptor HCA2-G signalling complex. Authors: Yang Yang / Hye Jin Kang / Ruogu Gao / Jingjing Wang / Gye Won Han / Jeffrey F DiBerto / Lijie Wu / Jiahui Tong / Lu Qu / Yiran Wu / Ryan Pileski / Xuemei Li / Xuejun Cai Zhang / Suwen Zhao ...Authors: Yang Yang / Hye Jin Kang / Ruogu Gao / Jingjing Wang / Gye Won Han / Jeffrey F DiBerto / Lijie Wu / Jiahui Tong / Lu Qu / Yiran Wu / Ryan Pileski / Xuemei Li / Xuejun Cai Zhang / Suwen Zhao / Terry Kenakin / Quan Wang / Raymond C Stevens / Wei Peng / Bryan L Roth / Zihe Rao / Zhi-Jie Liu / Abstract: The hydroxycarboxylic acid receptor 2 (HCA2) agonist niacin has been used as treatment for dyslipidemia for several decades albeit with skin flushing as a common side-effect in treated individuals. ...The hydroxycarboxylic acid receptor 2 (HCA2) agonist niacin has been used as treatment for dyslipidemia for several decades albeit with skin flushing as a common side-effect in treated individuals. Extensive efforts have been made to identify HCA2 targeting lipid lowering agents with fewer adverse effects, despite little being known about the molecular basis of HCA2 mediated signalling. Here, we report the cryo-electron microscopy structure of the HCA2-G signalling complex with the potent agonist MK-6892, along with crystal structures of HCA2 in inactive state. These structures, together with comprehensive pharmacological analysis, reveal the ligand binding mode and activation and signalling mechanisms of HCA2. This study elucidates the structural determinants essential for HCA2 mediated signalling and provides insights into ligand discovery for HCA2 and related receptors. | ||||||||||||||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 7xk2.cif.gz | 235.1 KB | Display | PDBx/mmCIF format |
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PDB format | pdb7xk2.ent.gz | 182.1 KB | Display | PDB format |
PDBx/mmJSON format | 7xk2.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 7xk2_validation.pdf.gz | 1.2 MB | Display | wwPDB validaton report |
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Full document | 7xk2_full_validation.pdf.gz | 1.2 MB | Display | |
Data in XML | 7xk2_validation.xml.gz | 45.7 KB | Display | |
Data in CIF | 7xk2_validation.cif.gz | 67.9 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/xk/7xk2 ftp://data.pdbj.org/pub/pdb/validation_reports/xk/7xk2 | HTTPS FTP |
-Related structure data
Related structure data | 33241MC 7zl9C 7zlyC 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
-Guanine nucleotide-binding protein ... , 3 types, 3 molecules ABC
#1: Protein | Mass: 40559.160 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: GNAI1 / Cell line (production host): HEK293 / Production host: Homo sapiens (human) / References: UniProt: P63096 |
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#2: Protein | Mass: 37416.930 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: GNB1 / Cell line (production host): HEK293 / Production host: Homo sapiens (human) / References: UniProt: P62873 |
#5: 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 / Cell line (production host): HEK293 / Production host: Homo sapiens (human) / References: UniProt: P59768 |
-Protein / Antibody / Non-polymers , 3 types, 3 molecules RS
#3: Protein | Mass: 38010.254 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: HCAR2 / Cell line (production host): HEK293 / Production host: Homo sapiens (human) / References: UniProt: Q8TDS4 |
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#4: Antibody | Mass: 26466.486 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Cell line (production host): HEK293 / Production host: Homo sapiens (human) |
#6: Chemical | ChemComp-FI7 / |
-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 |
-Sample preparation
Component | Name: Niacin Receptor HCA2-Gi complex / Type: COMPLEX / Entity ID: #1-#2, #4-#5 / Source: RECOMBINANT |
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Source (natural) | Organism: Homo sapiens (human) |
Source (recombinant) | Organism: Homo sapiens (human) / Cell: HEK293 |
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: FLOOD BEAM |
Electron lens | Mode: BRIGHT FIELD / Nominal defocus max: 2000 nm / Nominal defocus min: 1000 nm |
Image recording | Electron dose: 60 e/Å2 / Detector mode: SUPER-RESOLUTION / Film or detector model: GATAN K2 QUANTUM (4k x 4k) |
-Processing
Software |
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EM software | Name: cryoSPARC / Category: final Euler assignment | ||||||||||||||||||||||||
CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION | ||||||||||||||||||||||||
3D reconstruction | Resolution: 3.1 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 273841 / Symmetry type: POINT | ||||||||||||||||||||||||
Refinement | Cross valid method: THROUGHOUT | ||||||||||||||||||||||||
Displacement parameters | Biso max: 175.49 Å2 / Biso mean: 71.6689 Å2 / Biso min: 5.36 Å2 | ||||||||||||||||||||||||
Refine LS restraints |
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