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- PDB-6pb1: Cryo-EM structure of Urocortin 1-bound Corticotropin-releasing fa... -
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Open data
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Basic information
Entry | Database: PDB / ID: 6pb1 | |||||||||
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Title | Cryo-EM structure of Urocortin 1-bound Corticotropin-releasing factor 2 receptor in complex with Gs protein and Nb35 | |||||||||
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![]() | SIGNALING PROTEIN / Corticotropin-releasing factor 2 receptor / urocortins1 / Gs protein / GPCR | |||||||||
Function / homology | ![]() histone deacetylase inhibitor activity / corticotrophin-releasing factor receptor activity / corticotropin-releasing hormone receptor 2 binding / positive regulation of corticotropin secretion / positive regulation of behavioral fear response / negative regulation of hormone secretion / varicosity / response to auditory stimulus / drinking behavior / positive regulation of cAMP-mediated signaling ...histone deacetylase inhibitor activity / corticotrophin-releasing factor receptor activity / corticotropin-releasing hormone receptor 2 binding / positive regulation of corticotropin secretion / positive regulation of behavioral fear response / negative regulation of hormone secretion / varicosity / response to auditory stimulus / drinking behavior / positive regulation of cAMP-mediated signaling / negative regulation of appetite / corticotropin-releasing hormone receptor 1 binding / positive regulation of vascular permeability / neuropeptide hormone activity / negative regulation of cell size / G protein-coupled peptide receptor activity / Class B/2 (Secretin family receptors) / response to pain / negative regulation of feeding behavior / positive regulation of calcium ion import / startle response / peptide hormone binding / associative learning / PKA activation in glucagon signalling / social behavior / hair follicle placode formation / neuropeptide signaling pathway / developmental growth / D1 dopamine receptor binding / positive regulation of collagen biosynthetic process / intracellular transport / Synthesis, secretion, and deacylation of Ghrelin / Adenylate cyclase inhibitory pathway / positive regulation of protein localization to cell cortex / regulation of cAMP-mediated signaling / Hedgehog 'off' state / D2 dopamine receptor binding / G protein-coupled serotonin receptor binding / adenylate cyclase-activating adrenergic receptor signaling pathway / activation of adenylate cyclase activity / axon terminus / response to glucocorticoid / regulation of mitotic spindle organization / cellular response to forskolin / regulation of synaptic transmission, glutamatergic / positive regulation of cardiac muscle contraction / adenylate cyclase activator activity / negative regulation of blood pressure / aerobic respiration / adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway / trans-Golgi network membrane / positive regulation of DNA replication / Regulation of insulin secretion / G protein-coupled receptor binding / positive regulation of translation / female pregnancy / long-term synaptic potentiation / sensory perception of sound / G-protein beta/gamma-subunit complex binding / bone development / 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 / adenylate cyclase-activating G protein-coupled receptor signaling pathway / G protein-coupled acetylcholine receptor signaling pathway / G-protein activation / 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 / cognition / platelet aggregation / response to peptide hormone / 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 / positive regulation of interleukin-6 production / vasodilation / 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 Similarity search - Function | |||||||||
Biological species | ![]() synthetic construct (others) | |||||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 2.8 Å | |||||||||
![]() | 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. | |||||||||
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![]() | ![]() 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
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Structure viewer | Molecule: ![]() ![]() |
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Downloads & links
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PDBx/mmCIF format | ![]() | 206.8 KB | Display | ![]() |
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PDB format | ![]() | 167.2 KB | Display | ![]() |
PDBx/mmJSON format | ![]() | Tree view | ![]() | |
Others | ![]() |
-Validation report
Arichive directory | ![]() ![]() | HTTPS FTP |
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-Related structure data
Related structure data | ![]() 20285MC ![]() 6pb0C C: citing same article ( M: map data used to model this data |
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Similar structure data |
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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 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.) ![]() ![]() ![]() |
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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.) ![]() ![]() ![]() |
#5: Protein | Mass: 7861.143 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() |
-Protein / Protein/peptide / Antibody , 3 types, 3 molecules PUN
#1: Protein | Mass: 45116.375 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() |
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#2: Protein/peptide | Mass: 4703.277 Da / Num. of mol.: 1 / Source method: obtained synthetically / Source: (synth.) ![]() |
#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: ![]() ![]() |
-Non-polymers , 2 types, 9 molecules ![](data/chem/img/CLR.gif)
![](data/chem/img/PLM.gif)
![](data/chem/img/PLM.gif)
#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 |
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Sample preparation
Component | Name: Urocortin 1-bound corticotropin-releasing factor 2 receptor in complex with Gs protein Type: COMPLEX / Entity ID: #1-#6 / Source: RECOMBINANT |
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Source (natural) | Organism: ![]() |
Source (recombinant) | Organism: ![]() ![]() |
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 |
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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: 66 e/Å2 / Film or detector model: GATAN K2 BASE (4k x 4k) |
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Processing
Software | Name: PHENIX / Version: 1.13_2998: / Classification: refinement |
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CTF correction | Type: NONE |
3D reconstruction | Resolution: 2.8 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 67569 / Symmetry type: POINT |