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- PDB-7f6g: Cryo-EM structure of human angiotensin receptor AT1R in complex G... -
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Open data
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Basic information
Entry | Database: PDB / ID: 7f6g | |||||||||||||||||||||
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Title | Cryo-EM structure of human angiotensin receptor AT1R in complex Gq proteins and Sar1-AngII | |||||||||||||||||||||
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![]() | MEMBRANE PROTEIN / GPCR / angiotensin receptor | |||||||||||||||||||||
Function / homology | ![]() Fatty Acids bound to GPR40 (FFAR1) regulate insulin secretion / Acetylcholine regulates insulin secretion / PLC beta mediated events / phospholipase C-activating dopamine receptor signaling pathway / regulation of platelet activation / phototransduction, visible light / entrainment of circadian clock / glutamate receptor signaling pathway / regulation of canonical Wnt signaling pathway / action potential ...Fatty Acids bound to GPR40 (FFAR1) regulate insulin secretion / Acetylcholine regulates insulin secretion / PLC beta mediated events / phospholipase C-activating dopamine receptor signaling pathway / regulation of platelet activation / phototransduction, visible light / entrainment of circadian clock / glutamate receptor signaling pathway / regulation of canonical Wnt signaling pathway / action potential / : / photoreceptor outer segment / GTPase activator activity / G protein-coupled receptor binding / negative regulation of protein kinase 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 / G-protein activation / adenylate cyclase-activating G protein-coupled receptor signaling pathway / 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 / 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 / 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 / blood coagulation / 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 / G alpha (i) signalling events / fibroblast proliferation / G alpha (s) signalling events / G alpha (q) signalling events / nuclear membrane / cell population proliferation / Ras protein signal transduction / Extra-nuclear estrogen signaling / protein stabilization / G protein-coupled receptor signaling pathway / lysosomal membrane / GTPase activity / synapse / protein-containing complex binding / GTP binding / Golgi apparatus / signal transduction / extracellular exosome / membrane / metal ion binding / plasma membrane / cytoplasm / cytosol Similarity search - Function | |||||||||||||||||||||
Biological species | ![]() | |||||||||||||||||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 2.9 Å | |||||||||||||||||||||
![]() | Zhang, D. / Xu, L. / Zhan, Y. / Guo, J. / Zhang, H. | |||||||||||||||||||||
Funding support | ![]()
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![]() | ![]() Title: Structural insights into angiotensin receptor signaling modulation by balanced and biased agonists. Authors: Dongqi Zhang / Yongfeng Liu / Saheem A Zaidi / Lingyi Xu / Yuting Zhan / Anqi Chen / Jiangtao Guo / Xi-Ping Huang / Bryan L Roth / Vsevolod Katritch / Vadim Cherezov / Haitao Zhang / ![]() ![]() Abstract: The peptide hormone angiotensin II regulates blood pressure mainly through the type 1 angiotensin II receptor AT R and its downstream signaling proteins G and β-arrestin. AT R blockers, clinically ...The peptide hormone angiotensin II regulates blood pressure mainly through the type 1 angiotensin II receptor AT R and its downstream signaling proteins G and β-arrestin. AT R blockers, clinically used as antihypertensive drugs, inhibit both signaling pathways, whereas AT R β-arrestin-biased agonists have shown great potential for the treatment of acute heart failure. Here, we present a cryo-electron microscopy (cryo-EM) structure of the human AT R in complex with a balanced agonist, Sar -AngII, and G protein at 2.9 Å resolution. This structure, together with extensive functional assays and computational modeling, reveals the molecular mechanisms for AT R signaling modulation and suggests that a major hydrogen bond network (MHN) inside the receptor serves as a key regulator of AT R signal transduction from the ligand-binding pocket to both G and β-arrestin pathways. Specifically, we found that the MHN mutations N111 A and N294 A induce biased signaling to G and β-arrestin, respectively. These insights should facilitate AT R structure-based drug discovery for the treatment of cardiovascular diseases. | |||||||||||||||||||||
History |
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Structure visualization
Structure viewer | Molecule: ![]() ![]() |
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Downloads & links
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Download
PDBx/mmCIF format | ![]() | 218.8 KB | Display | ![]() |
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PDB format | ![]() | 165.1 KB | Display | ![]() |
PDBx/mmJSON format | ![]() | Tree view | ![]() | |
Others | ![]() |
-Validation report
Summary document | ![]() | 1.1 MB | Display | ![]() |
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Full document | ![]() | 1.1 MB | Display | |
Data in XML | ![]() | 34.5 KB | Display | |
Data in CIF | ![]() | 52.2 KB | Display | |
Arichive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 31479MC M: map data used to model this data C: citing same article ( |
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Similar structure data | Similarity search - Function & homology ![]() |
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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 BCD
#3: Protein | Mass: 43534.449 Da / Num. of mol.: 1 / Mutation: R183Q, Q209L Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() |
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#4: Protein | Mass: 39086.641 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() |
#5: Protein | Mass: 9242.612 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() |
-Protein / Protein/peptide / Sugars / Non-polymers , 4 types, 9 molecules AL![](data/chem/img/NAG.gif)
![](data/chem/img/CLR.gif)
![](data/chem/img/NAG.gif)
![](data/chem/img/CLR.gif)
#1: Protein | Mass: 81574.406 Da / Num. of mol.: 1 / Mutation: F77A, N295A Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() |
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#2: Protein/peptide | Mass: 1004.185 Da / Num. of mol.: 1 / Source method: obtained synthetically Details: This peptide Sar1-AngII is the ligand of the protein angiotensin receptor. Source: (synth.) ![]() |
#6: Sugar | ChemComp-NAG / |
#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: Angiotensin receptor AT1R in complex with Gq proteins and Sar1-AngII Type: COMPLEX / Entity ID: #1-#5 / Source: RECOMBINANT |
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Molecular weight | Value: 0.168 MDa / Experimental value: YES |
Source (natural) | Organism: ![]() |
Source (recombinant) | Organism: ![]() ![]() |
Buffer solution | pH: 7.5 |
Specimen | Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES |
Vitrification | Cryogen name: ETHANE |
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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 |
Image recording | Electron dose: 64 e/Å2 / Film or detector model: GATAN K2 BASE (4k x 4k) |
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Processing
Software | Name: PHENIX / Version: 1.19.2_4158: / Classification: refinement | ||||||||||||||||||||||||
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CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION | ||||||||||||||||||||||||
3D reconstruction | Resolution: 2.9 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 2380323 / Symmetry type: POINT | ||||||||||||||||||||||||
Refine LS restraints |
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