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Open data
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Basic information
| Entry | Database: PDB / ID: 6p9x | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Title | CRF1 Receptor Gs GPCR protein complex with CRF1 peptide | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Components |
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Keywords | MEMBRANE PROTEIN / GPCR | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Function / homology | Function and homology informationcorticotropin-releasing hormone activity / positive regulation of digestive system process / diterpenoid metabolic process / corticotropin-releasing hormone binding / positive regulation of circadian sleep/wake cycle, wakefulness / negative regulation of circadian sleep/wake cycle, REM sleep / regulation of corticosterone secretion / corticotrophin-releasing factor receptor activity / corticotropin-releasing hormone receptor activity / corticotropin-releasing hormone receptor 2 binding ...corticotropin-releasing hormone activity / positive regulation of digestive system process / diterpenoid metabolic process / corticotropin-releasing hormone binding / positive regulation of circadian sleep/wake cycle, wakefulness / negative regulation of circadian sleep/wake cycle, REM sleep / regulation of corticosterone secretion / corticotrophin-releasing factor receptor activity / corticotropin-releasing hormone receptor activity / corticotropin-releasing hormone receptor 2 binding / positive regulation of corticosterone secretion / negative regulation of voltage-gated calcium channel activity / corticotropin secretion / positive regulation of cortisol secretion / positive regulation of corticotropin secretion / negative regulation of glucagon secretion / positive regulation of behavioral fear response / general adaptation syndrome, behavioral process / cellular response to corticotropin-releasing hormone stimulus / MECP2 regulates transcription of neuronal ligands / parturition / glucocorticoid biosynthetic process / regulation of serotonin secretion / hormone-mediated apoptotic signaling pathway / monoatomic ion homeostasis / neuronal dense core vesicle lumen / negative regulation of norepinephrine secretion / varicosity / negative regulation of epinephrine secretion / negative regulation of luteinizing hormone secretion / response to ether / neuropeptide hormone activity / synaptic transmission, dopaminergic / fear response / corticotropin-releasing hormone receptor 1 binding / behavioral response to ethanol / response to aldosterone / Class B/2 (Secretin family receptors) / negative regulation of systemic arterial blood pressure / G protein-coupled peptide receptor activity / regulation of NMDA receptor activity / cellular response to cocaine / adrenal gland development / response to pain / response to corticosterone / positive regulation of calcium ion import / hypothalamus development / response to immobilization stress / adenylate cyclase-activating G protein-coupled bile acid receptor signaling pathway / adenylate cyclase-activating serotonin receptor signaling pathway / exploration behavior / positive regulation of cAMP/PKA signal transduction / locomotory exploration behavior / regulation of skeletal muscle contraction / PKA activation in glucagon signalling / associative learning / hair follicle placode formation / developmental growth / cellular response to dexamethasone stimulus / intracellular transport / D1 dopamine receptor binding / vascular endothelial cell response to laminar fluid shear stress / renal water homeostasis / activation of adenylate cyclase activity / Hedgehog 'off' state / cellular response to acidic pH / adenylate cyclase-activating adrenergic receptor signaling pathway / cellular response to glucagon stimulus / lung development / intracellular glucose homeostasis / adenylate cyclase activator activity / positive regulation of insulin secretion involved in cellular response to glucose stimulus / trans-Golgi network membrane / negative regulation of inflammatory response to antigenic stimulus / response to prostaglandin E / female pregnancy / hormone activity / bone development / postsynaptic density membrane / response to estrogen / platelet aggregation / G protein-coupled receptor activity / cognition / G-protein beta/gamma-subunit complex binding / Olfactory Signaling Pathway / Activation of the phototransduction cascade / G protein-coupled acetylcholine receptor signaling pathway / G beta:gamma signalling through PLC beta / Presynaptic function of Kainate receptors / Thromboxane signalling through TP receptor / positive regulation of insulin secretion / Activation of G protein gated Potassium channels / Inhibition of voltage gated Ca2+ channels via Gbeta/gamma subunits / G-protein activation / Glucagon signaling in metabolic regulation / G beta:gamma signalling through CDC42 / Prostacyclin signalling through prostacyclin receptor / G beta:gamma signalling through BTK / Synthesis, secretion, and inactivation of Glucagon-like Peptide-1 (GLP-1) / photoreceptor disc membrane Similarity search - Function | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Biological species | Homo sapiens (human)![]() | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 2.91 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Authors | Belousoff, M.J. / Liang, Y.L. / Sexton, P. / Danev, R. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Funding support | Australia, Japan, 5items
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Citation | Journal: Mol Cell / Year: 2020Title: Toward a Structural Understanding of Class B GPCR Peptide Binding and Activation. Authors: Yi-Lynn Liang / Matthew J Belousoff / Peishen Zhao / Cassandra Koole / Madeleine M Fletcher / Tin T Truong / Villy Julita / George Christopoulos / H Eric Xu / Yan Zhang / Maryam Khoshouei / ...Authors: Yi-Lynn Liang / Matthew J Belousoff / Peishen Zhao / Cassandra Koole / Madeleine M Fletcher / Tin T Truong / Villy Julita / George Christopoulos / H Eric Xu / Yan Zhang / Maryam Khoshouei / Arthur Christopoulos / Radostin Danev / Patrick M Sexton / Denise Wootten / ![]() Abstract: Class B G protein-coupled receptors (GPCRs) are important therapeutic targets for major diseases. Here, we present structures of peptide and Gs-bound pituitary adenylate cyclase-activating peptide, ...Class B G protein-coupled receptors (GPCRs) are important therapeutic targets for major diseases. Here, we present structures of peptide and Gs-bound pituitary adenylate cyclase-activating peptide, PAC1 receptor, and corticotropin-releasing factor (CRF), (CRF1) receptor. Together with recently solved structures, these provide coverage of the major class B GPCR subfamilies. Diverse orientations of the extracellular domain to the receptor core in different receptors are at least partially dependent on evolutionary conservation in the structure and nature of peptide interactions. Differences in peptide interactions to the receptor core also influence the interlinked TM2-TM1-TM6/ECL3/TM7 domain, and this is likely important in their diverse signaling. However, common conformational reorganization of ECL2, linked to reorganization of ICL2, modulates G protein contacts. Comparison between receptors reveals ICL2 as a key domain forming dynamic G protein interactions in a receptor- and ligand-specific manner. This work advances our understanding of class B GPCR activation and Gs coupling. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Structure visualization
| Movie |
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| Structure viewer | Molecule: Molmil Jmol/JSmol |
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Downloads & links
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Download
| PDBx/mmCIF format | 6p9x.cif.gz | 203.6 KB | Display | PDBx/mmCIF format |
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| PDB format | pdb6p9x.ent.gz | 152.9 KB | Display | PDB format |
| PDBx/mmJSON format | 6p9x.json.gz | Tree view | PDBx/mmJSON format | |
| Others | Other downloads |
-Validation report
| Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/p9/6p9x ftp://data.pdbj.org/pub/pdb/validation_reports/p9/6p9x | HTTPS FTP |
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-Related structure data
| Related structure data | ![]() 20277MC ![]() 0993C ![]() 6p9yC M: map data used to model this data C: citing same article ( |
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| Similar structure data | |
| EM raw data | EMPIAR-10361 (Title: Cryo-EM of CRF1 receptor bound to CRF and Gs protein / Data size: 2.6 TBData #1: Unaligned multi-frame gain-normalized movies in LZW compressed TIFF format [micrographs - multiframe]) |
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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
| #1: Protein | Mass: 45700.418 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: GNAS, GNAS1, GSP / Production host: Trichoplusia ni (cabbage looper) / References: UniProt: P63092 |
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| #2: Protein | Mass: 38534.062 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: GNB1 / Production host: Trichoplusia ni (cabbage looper) / References: UniProt: P62873 |
| #3: 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: Trichoplusia ni (cabbage looper) / References: UniProt: P59768 |
-Antibody / Protein / Protein/peptide / Non-polymers , 4 types, 20 molecules NRP

| #4: Antibody | Mass: 15140.742 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() |
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| #5: Protein | Mass: 49392.109 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: Trichoplusia ni (cabbage looper) / References: UniProt: P34998 |
| #6: Protein/peptide | Mass: 4764.481 Da / Num. of mol.: 1 / Source method: obtained synthetically / Source: (synth.) Homo sapiens (human) / References: UniProt: P06850 |
| #7: Water | ChemComp-HOH / |
-Details
| Has protein modification | 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
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| Molecular weight | Experimental value: NO | ||||||||||||||||||||||||||||||
| Source (natural) |
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| Source (recombinant) |
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| Buffer solution | pH: 7.4 | ||||||||||||||||||||||||||||||
| 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: FIELD EMISSION GUN / Accelerating voltage: 300 kV / Illumination mode: SPOT SCAN |
| Electron lens | Mode: BRIGHT FIELD / Cs: 2.7 mm |
| Image recording | Average exposure time: 3.7 sec. / Electron dose: 1 e/Å2 / Film or detector model: GATAN K3 (6k x 4k) / Num. of grids imaged: 1 |
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Processing
| Software | Name: PHENIX / Version: 1.15.2_3472: / Classification: refinement | ||||||||||||||||||||||||
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| EM software | Name: PHENIX / Category: model refinement | ||||||||||||||||||||||||
| CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION | ||||||||||||||||||||||||
| Symmetry | Point symmetry: C1 (asymmetric) | ||||||||||||||||||||||||
| 3D reconstruction | Resolution: 2.91 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 516000 / Symmetry type: POINT | ||||||||||||||||||||||||
| Refine LS restraints |
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Movie
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About Yorodumi




Homo sapiens (human)

Australia,
Japan, 5items
Citation
UCSF Chimera














PDBj





















Trichoplusia ni (cabbage looper)

