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Yorodumi- PDB-7f2o: Cryo-EM structure of the type 2 bradykinin receptor in complex wi... -
+Open data
-Basic information
Entry | Database: PDB / ID: 7f2o | |||||||||||||||||||||
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Title | Cryo-EM structure of the type 2 bradykinin receptor in complex with the bradykinin and an Gq protein | |||||||||||||||||||||
Components |
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Keywords | MEMBRANE PROTEIN / GPCR / Complex | |||||||||||||||||||||
Function / homology | Function and homology information negative regulation of intrinsic apoptotic signaling pathway in response to osmotic stress by p53 class mediator / bradykinin receptor activity / regulation of vascular permeability / phosphatidylinositol phospholipase C activity / G-protein activation / Activation of the phototransduction cascade / Glucagon-type ligand receptors / Thromboxane signalling through TP receptor / Sensory perception of sweet, bitter, and umami (glutamate) taste / G beta:gamma signalling through PI3Kgamma ...negative regulation of intrinsic apoptotic signaling pathway in response to osmotic stress by p53 class mediator / bradykinin receptor activity / regulation of vascular permeability / phosphatidylinositol phospholipase C activity / G-protein activation / Activation of the phototransduction cascade / Glucagon-type ligand receptors / Thromboxane signalling through TP receptor / Sensory perception of sweet, bitter, and umami (glutamate) taste / G beta:gamma signalling through PI3Kgamma / G beta:gamma signalling through CDC42 / vasoconstriction / Ca2+ pathway / Cooperation of PDCL (PhLP1) and TRiC/CCT in G-protein beta folding / Activation of G protein gated Potassium channels / Inhibition of voltage gated Ca2+ channels via Gbeta/gamma subunits / G alpha (z) signalling events / Vasopressin regulates renal water homeostasis via Aquaporins / Glucagon-like Peptide-1 (GLP1) regulates insulin secretion / type 1 angiotensin receptor binding / Adrenaline,noradrenaline inhibits insulin secretion / ADP signalling through P2Y purinoceptor 12 / blood circulation / G alpha (q) signalling events / Thrombin signalling through proteinase activated receptors (PARs) / G alpha (i) signalling events / Activation of G protein gated Potassium channels / G-protein activation / G beta:gamma signalling through PI3Kgamma / Prostacyclin signalling through prostacyclin receptor / G beta:gamma signalling through PLC beta / ADP signalling through P2Y purinoceptor 1 / Thromboxane signalling through TP receptor / Presynaptic function of Kainate receptors / G beta:gamma signalling through CDC42 / Inhibition of voltage gated Ca2+ channels via Gbeta/gamma subunits / Glucagon-type ligand receptors / Adrenaline,noradrenaline inhibits insulin secretion / G alpha (12/13) signalling events / G beta:gamma signalling through BTK / ADP signalling through P2Y purinoceptor 12 / alkylglycerophosphoethanolamine phosphodiesterase activity / Cooperation of PDCL (PhLP1) and TRiC/CCT in G-protein beta folding / Thrombin signalling through proteinase activated receptors (PARs) / Ca2+ pathway / G alpha (z) signalling events / Extra-nuclear estrogen signaling / G alpha (s) signalling events / G alpha (q) signalling events / photoreceptor outer segment membrane / arachidonate secretion / G alpha (i) signalling events / Glucagon-like Peptide-1 (GLP1) regulates insulin secretion / spectrin binding / Vasopressin regulates renal water homeostasis via Aquaporins / plasma membrane => GO:0005886 / negative regulation of peptidyl-serine phosphorylation / smooth muscle contraction / photoreceptor outer segment / regulation of vasoconstriction / cell surface receptor protein tyrosine kinase signaling pathway / cardiac muscle cell apoptotic process / response to salt stress / photoreceptor inner segment / Peptide ligand-binding receptors / G protein-coupled receptor activity / cellular response to catecholamine stimulus / vasodilation / sensory perception of taste / adenylate cyclase-activating dopamine receptor signaling pathway / cellular response to prostaglandin E stimulus / G-protein beta-subunit binding / heterotrimeric G-protein complex / signaling receptor complex adaptor activity / GTPase binding / retina development in camera-type eye / phospholipase C-activating G protein-coupled receptor signaling pathway / positive regulation of cytosolic calcium ion concentration / G alpha (i) signalling events / cellular response to hypoxia / cell body / protease binding / G alpha (q) signalling events / cell population proliferation / cell surface receptor signaling pathway / endosome / inflammatory response / G protein-coupled receptor signaling pathway / protein heterodimerization activity / intracellular membrane-bounded organelle / GTPase activity / dendrite / synapse / protein-containing complex binding / Golgi apparatus / membrane / plasma membrane / cytoplasm Similarity search - Function | |||||||||||||||||||||
Biological species | Homo sapiens (human) Rattus norvegicus (Norway rat) synthetic construct (others) Bos taurus (cattle) | |||||||||||||||||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 2.9 Å | |||||||||||||||||||||
Authors | Yin, Y. / Jiang, Y. | |||||||||||||||||||||
Funding support | China, 6items
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Citation | Journal: Nat Struct Mol Biol / Year: 2021 Title: Molecular basis for kinin selectivity and activation of the human bradykinin receptors. Authors: Yu-Ling Yin / Chenyu Ye / Fulai Zhou / Jia Wang / Dehua Yang / Wanchao Yin / Ming-Wei Wang / H Eric Xu / Yi Jiang / Abstract: Bradykinin and kallidin are endogenous kinin peptide hormones that belong to the kallikrein-kinin system and are essential to the regulation of blood pressure, inflammation, coagulation and pain ...Bradykinin and kallidin are endogenous kinin peptide hormones that belong to the kallikrein-kinin system and are essential to the regulation of blood pressure, inflammation, coagulation and pain control. Des-Arg-kallidin, the carboxy-terminal des-Arg metabolite of kallidin, and bradykinin selectively activate two G protein-coupled receptors, type 1 and type 2 bradykinin receptors (B1R and B2R), respectively. The hyperactivation of bradykinin receptors, termed 'bradykinin storm', is associated with pulmonary edema in COVID-19 patients, suggesting that bradykinin receptors are important targets for COVID-19 intervention. Here we report two G protein-coupled complex structures of human B1R and B2R bound to des-Arg-kallidin and bradykinin, respectively. Combined with functional analysis, our structures reveal the mechanism of ligand selectivity and specific activation of the bradykinin receptor. These findings also provide a framework for guiding drug design targeting bradykinin receptors for the treatment of inflammation, cardiovascular disorders and COVID-19. | |||||||||||||||||||||
History |
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-Structure visualization
Movie |
Movie viewer |
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Structure viewer | Molecule: MolmilJmol/JSmol |
-Downloads & links
-Download
PDBx/mmCIF format | 7f2o.cif.gz | 221.1 KB | Display | PDBx/mmCIF format |
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PDB format | pdb7f2o.ent.gz | 173.1 KB | Display | PDB format |
PDBx/mmJSON format | 7f2o.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 7f2o_validation.pdf.gz | 712.9 KB | Display | wwPDB validaton report |
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Full document | 7f2o_full_validation.pdf.gz | 720 KB | Display | |
Data in XML | 7f2o_validation.xml.gz | 33.8 KB | Display | |
Data in CIF | 7f2o_validation.cif.gz | 52.3 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/f2/7f2o ftp://data.pdbj.org/pub/pdb/validation_reports/f2/7f2o | HTTPS FTP |
-Related structure data
Related structure data | 31429MC 7eibC M: map data used to model this data C: citing same article (ref.) |
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Similar structure data |
-Links
-Assembly
Deposited unit |
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-Components
-Protein , 2 types, 2 molecules AR
#1: Protein | Mass: 41724.383 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Production host: Spodoptera frugiperda (fall armyworm) |
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#4: Protein | Mass: 67152.914 Da / Num. of mol.: 1 / Mutation: C146W Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: BDKRB2, BKR2 / Production host: Spodoptera frugiperda (fall armyworm) / References: UniProt: P30411 |
-Guanine nucleotide-binding protein ... , 2 types, 2 molecules BY
#2: Protein | Mass: 41055.867 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Rattus norvegicus (Norway rat) / Gene: Gnb1 / Production host: Spodoptera frugiperda (fall armyworm) / References: UniProt: P54311 |
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#6: Protein | Mass: 7861.143 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Bos taurus (cattle) / Gene: GNG2 / Production host: Spodoptera frugiperda (fall armyworm) / References: UniProt: P63212 |
-Protein/peptide / Antibody , 2 types, 2 molecules DS
#3: Protein/peptide | Mass: 1062.224 Da / Num. of mol.: 1 / Source method: obtained synthetically / Source: (synth.) Homo sapiens (human) |
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#5: Antibody | Mass: 26392.385 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) synthetic construct (others) / Production host: Spodoptera frugiperda (fall armyworm) |
-Details
Has ligand of interest | N |
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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 |
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Source (natural) |
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Source (recombinant) |
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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: OTHER / Accelerating voltage: 300 kV / Illumination mode: OTHER |
Electron lens | Mode: BRIGHT FIELD |
Image recording | Electron dose: 80 e/Å2 / Film or detector model: OTHER |
-Processing
Software | Name: PHENIX / Version: 1.18.2_3874: / Classification: refinement | ||||||||||||||||||||||||
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CTF correction | Type: NONE | ||||||||||||||||||||||||
3D reconstruction | Resolution: 2.9 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 664416 / Symmetry type: POINT | ||||||||||||||||||||||||
Refine LS restraints |
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