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Yorodumi- PDB-6pb0: Cryo-EM structure of Urocortin 1-bound Corticotropin-releasing fa... -
+Open data
-Basic information
Entry | Database: PDB / ID: 6pb0 | |||||||||
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Title | Cryo-EM structure of Urocortin 1-bound Corticotropin-releasing factor 1 receptor in complex with Gs protein and Nb35 | |||||||||
Components |
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Keywords | SIGNALING PROTEIN / Corticotropin-releasing factor 1 receptor / urocortins1 / Gs protein / GPCR | |||||||||
Function / homology | Function and homology information regulation of adenylate cyclase activity involved in G protein-coupled receptor signaling pathway / corticotropin-releasing hormone binding / histone deacetylase inhibitor activity / regulation of corticosterone secretion / corticotrophin-releasing factor receptor activity / corticotropin-releasing hormone receptor activity / corticotropin-releasing hormone receptor 2 binding / corticotropin secretion / positive regulation of corticotropin secretion / general adaptation syndrome, behavioral process ...regulation of adenylate cyclase activity involved in G protein-coupled receptor signaling pathway / corticotropin-releasing hormone binding / histone deacetylase inhibitor activity / regulation of corticosterone secretion / corticotrophin-releasing factor receptor activity / corticotropin-releasing hormone receptor activity / corticotropin-releasing hormone receptor 2 binding / corticotropin secretion / positive regulation of corticotropin secretion / general adaptation syndrome, behavioral process / positive regulation of behavioral fear response / parturition / cellular response to corticotropin-releasing hormone stimulus / negative regulation of hormone secretion / negative regulation of voltage-gated calcium channel activity / varicosity / behavioral response to ethanol / response to auditory stimulus / drinking behavior / positive regulation of cAMP-mediated signaling / negative regulation of appetite / positive regulation of vascular permeability / fear response / neuropeptide hormone activity / negative regulation of cell size / G protein-coupled peptide receptor activity / Class B/2 (Secretin family receptors) / exploration behavior / adrenal gland development / response to pain / negative regulation of feeding behavior / positive regulation of calcium ion import / startle response / associative learning / PKA activation in glucagon signalling / social behavior / hair follicle placode formation / mu-type opioid receptor binding / developmental growth / corticotropin-releasing hormone receptor 1 binding / positive regulation of collagen biosynthetic process / intracellular transport / Adenylate cyclase inhibitory pathway / D1 dopamine receptor binding / Synthesis, secretion, and deacylation of Ghrelin / positive regulation of protein localization to cell cortex / neuropeptide signaling pathway / regulation of cAMP-mediated signaling / D2 dopamine receptor binding / Hedgehog 'off' state / G protein-coupled serotonin receptor binding / beta-2 adrenergic receptor binding / axon terminus / adenylate cyclase-activating adrenergic receptor signaling pathway / response to glucocorticoid / regulation of mitotic spindle organization / cellular response to forskolin / regulation of synaptic transmission, glutamatergic / positive regulation of cardiac muscle contraction / activation of adenylate cyclase activity / adenylate cyclase activator activity / adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway / negative regulation of blood pressure / aerobic respiration / trans-Golgi network membrane / positive regulation of DNA replication / Regulation of insulin secretion / positive regulation of translation / G protein-coupled receptor binding / female pregnancy / sensory perception of sound / insulin-like growth factor receptor binding / ionotropic glutamate receptor binding / G-protein beta/gamma-subunit complex binding / Olfactory Signaling Pathway / Activation of the phototransduction cascade / bone development / 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 / adenylate cyclase-activating G protein-coupled receptor signaling pathway / 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) / cognition / 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 / platelet aggregation / Vasopressin regulates renal water homeostasis via Aquaporins Similarity search - Function | |||||||||
Biological species | Homo sapiens (human) synthetic construct (others) | |||||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3 Å | |||||||||
Authors | Ma, S. / Shen, Q. / Zhao, L.-H. / Mao, C. / Zhou, X.E. / Shen, D.-D. / de Waal, P.W. / Bi, P. / Li, C. / Jiang, Y. ...Ma, S. / Shen, Q. / Zhao, L.-H. / Mao, C. / Zhou, X.E. / Shen, D.-D. / de Waal, P.W. / Bi, P. / Li, C. / Jiang, Y. / Wang, M.-W. / Sexton, P.M. / Wootten, D. / Melcher, K. / Zhang, Y. / Xu, H.E. | |||||||||
Funding support | United States, China, 2items
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Citation | Journal: Mol Cell / Year: 2020 Title: Molecular Basis for Hormone Recognition and Activation of Corticotropin-Releasing Factor Receptors. Authors: Shanshan Ma / Qingya Shen / Li-Hua Zhao / Chunyou Mao / X Edward Zhou / Dan-Dan Shen / Parker W de Waal / Peng Bi / Chuntao Li / Yi Jiang / Ming-Wei Wang / Patrick M Sexton / Denise Wootten ...Authors: Shanshan Ma / Qingya Shen / Li-Hua Zhao / Chunyou Mao / X Edward Zhou / Dan-Dan Shen / Parker W de Waal / Peng Bi / Chuntao Li / Yi Jiang / Ming-Wei Wang / Patrick M Sexton / Denise Wootten / Karsten Melcher / Yan Zhang / H Eric Xu / Abstract: Corticotropin-releasing factor (CRF) and the three related peptides urocortins 1-3 (UCN1-UCN3) are endocrine hormones that control the stress responses by activating CRF1R and CRF2R, two members of ...Corticotropin-releasing factor (CRF) and the three related peptides urocortins 1-3 (UCN1-UCN3) are endocrine hormones that control the stress responses by activating CRF1R and CRF2R, two members of class B G-protein-coupled receptors (GPCRs). Here, we present two cryoelectron microscopy (cryo-EM) structures of UCN1-bound CRF1R and CRF2R with the stimulatory G protein. In both structures, UCN1 adopts a single straight helix with its N terminus dipped into the receptor transmembrane bundle. Although the peptide-binding residues in CRF1R and CRF2R are different from other members of class B GPCRs, the residues involved in receptor activation and G protein coupling are conserved. In addition, both structures reveal bound cholesterol molecules to the receptor transmembrane helices. Our structures define the basis of ligand-binding specificity in the CRF receptor-hormone system, establish a common mechanism of class B GPCR activation and G protein coupling, and provide a paradigm for studying membrane protein-lipid interactions for class B GPCRs. | |||||||||
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 | 6pb0.cif.gz | 207.9 KB | Display | PDBx/mmCIF format |
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PDB format | pdb6pb0.ent.gz | 168.5 KB | Display | PDB format |
PDBx/mmJSON format | 6pb0.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 6pb0_validation.pdf.gz | 1.2 MB | Display | wwPDB validaton report |
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Full document | 6pb0_full_validation.pdf.gz | 1.2 MB | Display | |
Data in XML | 6pb0_validation.xml.gz | 34.7 KB | Display | |
Data in CIF | 6pb0_validation.cif.gz | 51.9 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/pb/6pb0 ftp://data.pdbj.org/pub/pdb/validation_reports/pb/6pb0 | HTTPS FTP |
-Related structure data
Related structure data | 20284MC 6pb1C 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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1 |
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-Components
-Guanine nucleotide-binding protein ... , 3 types, 3 molecules ABG
#3: Protein | Mass: 43897.789 Da / Num. of mol.: 1 / Mutation: A212G, S352A Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: GNAS, GNAS1, GSP, GNAI1 / Production host: Spodoptera frugiperda (fall armyworm) / References: UniProt: P63092, UniProt: P63096 |
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#4: Protein | Mass: 37915.496 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 |
#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 / Production host: Spodoptera frugiperda (fall armyworm) / References: UniProt: P59768 |
-Protein / Protein/peptide / Antibody , 3 types, 3 molecules RUN
#1: Protein | Mass: 43509.711 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: CRHR1, CRFR, CRFR1, CRHR Production host: Spodoptera aff. frugiperda 2 RZ-2014 (butterflies/moths) References: UniProt: P34998 |
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#2: Protein/peptide | Mass: 4703.277 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: UCN / Production host: synthetic construct (others) / References: UniProt: P55089 |
#6: Antibody | Mass: 15343.019 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) synthetic construct (others) / Production host: Escherichia coli (E. coli) |
-Non-polymers , 2 types, 12 molecules
#7: Chemical | ChemComp-CLR / #8: Chemical | ChemComp-PLM / |
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-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 | Name: Urocortin1-bound CRF1R in complex Gs and Nb35 / Type: COMPLEX / Entity ID: #1-#6 / Source: RECOMBINANT |
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Source (natural) | Organism: Homo sapiens (human) |
Source (recombinant) | Organism: Spodoptera frugiperda (fall armyworm) |
Buffer solution | pH: 7.4 |
Specimen | Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES |
Specimen support | Details: unspecified |
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 |
Image recording | Electron dose: 66 e/Å2 / Film or detector model: GATAN K2 BASE (4k x 4k) |
-Processing
Software | Name: PHENIX / Version: 1.13_2998: / Classification: refinement |
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CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION |
3D reconstruction | Resolution: 3 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 97386 / Symmetry type: POINT |