+Open data
-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 information corticotropin-releasing hormone activity / positive regulation of digestive system process / positive regulation of corticosterone secretion / : / 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 2 binding ...corticotropin-releasing hormone activity / positive regulation of digestive system process / positive regulation of corticosterone secretion / : / 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 2 binding / corticotropin secretion / negative regulation of glucagon secretion / positive regulation of corticotropin secretion / positive regulation of cortisol secretion / regulation of serotonin secretion / MECP2 regulates transcription of neuronal ligands / general adaptation syndrome, behavioral process / positive regulation of behavioral fear response / cellular response to corticotropin-releasing hormone stimulus / glucocorticoid biosynthetic process / negative regulation of norepinephrine secretion / parturition / hormone-mediated apoptotic signaling pathway / negative regulation of luteinizing hormone secretion / monoatomic ion homeostasis / negative regulation of epinephrine secretion / varicosity / negative regulation of voltage-gated calcium channel activity / behavioral response to ethanol / positive regulation of cAMP-mediated signaling / fear response / response to ether / corticotropin-releasing hormone receptor 1 binding / neuropeptide hormone activity / synaptic transmission, dopaminergic / G protein-coupled peptide receptor activity / negative regulation of systemic arterial blood pressure / Class B/2 (Secretin family receptors) / regulation of NMDA receptor activity / cellular response to cocaine / diterpenoid metabolic process / exploration behavior / adrenal gland development / response to corticosterone / response to aldosterone / activation of adenylate cyclase activity / hypothalamus development / response to pain / positive regulation of calcium ion import / positive regulation of insulin secretion involved in cellular response to glucose stimulus / locomotory exploration behavior / associative learning / response to immobilization stress / cellular response to dexamethasone stimulus / female pregnancy / long-term synaptic potentiation / adenylate cyclase-activating G protein-coupled receptor signaling pathway / lung development / Olfactory Signaling Pathway / Activation of the phototransduction cascade / hormone activity / Prostacyclin signalling through prostacyclin receptor / G beta:gamma signalling through PLC beta / Presynaptic function of Kainate receptors / Thromboxane signalling through TP receptor / Glucagon signaling in metabolic regulation / 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 / G beta:gamma signalling through CDC42 / Vasopressin regulates renal water homeostasis via Aquaporins / G beta:gamma signalling through BTK / ADP signalling through P2Y purinoceptor 12 / Synthesis, secretion, and inactivation of Glucagon-like Peptide-1 (GLP-1) / Glucagon-type ligand receptors / Sensory perception of sweet, bitter, and umami (glutamate) taste / photoreceptor disc membrane / G alpha (z) signalling events / Adrenaline,noradrenaline inhibits insulin secretion / Glucagon-like Peptide-1 (GLP1) regulates insulin secretion / ADORA2B mediated anti-inflammatory cytokines production / response to estrogen / cellular response to catecholamine stimulus / sensory perception of taste / ADP signalling through P2Y purinoceptor 1 / adenylate cyclase-activating dopamine receptor signaling pathway / G beta:gamma signalling through PI3Kgamma / GPER1 signaling / Cooperation of PDCL (PhLP1) and TRiC/CCT in G-protein beta folding / cellular response to prostaglandin E stimulus / Inactivation, recovery and regulation of the phototransduction cascade / G-protein beta-subunit binding / heterotrimeric G-protein complex / G alpha (12/13) signalling events / extracellular vesicle / signaling receptor complex adaptor activity / Thrombin signalling through proteinase activated receptors (PARs) / GTPase binding / retina development in camera-type eye Similarity search - Function | ||||||||||||||||||
Biological species | Homo sapiens (human) Lama glama (llama) | ||||||||||||||||||
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: 2020 Title: 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. | ||||||||||||||||||
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 | 6p9x.cif.gz | 203.1 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
Summary document | 6p9x_validation.pdf.gz | 1.1 MB | Display | wwPDB validaton report |
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Full document | 6p9x_full_validation.pdf.gz | 1.1 MB | Display | |
Data in XML | 6p9x_validation.xml.gz | 36.6 KB | Display | |
Data in CIF | 6p9x_validation.cif.gz | 56.8 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/p9/6p9x ftp://data.pdbj.org/pub/pdb/validation_reports/p9/6p9x | HTTPS FTP |
-Related structure data
Related structure data | 20277MC 0993C 6p9yC M: map data used to model this data C: citing same article (ref.) |
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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 TB Data #1: Unaligned multi-frame gain-normalized movies in LZW compressed TIFF format [micrographs - multiframe]) |
-Links
-Assembly
Deposited unit |
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1 |
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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.) Lama glama (llama) / Production host: Escherichia coli (E. coli) |
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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 |
-Sample preparation
Component |
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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 |
-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 |
-Processing
Software | Name: PHENIX / Version: 1.15.2_3472: / Classification: refinement | ||||||||||||||||||||||||
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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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