+Open data
-Basic information
Entry | Database: PDB / ID: 6p9x | ||||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Title | CRF1 Receptor Gs GPCR protein complex with CRF1 peptide | ||||||||||||||||||
Components |
| ||||||||||||||||||
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 / regulation of adenylate cyclase activity involved in G protein-coupled receptor signaling pathway / 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 / regulation of serotonin secretion / corticotrophin-releasing factor receptor activity ...corticotropin-releasing hormone activity / positive regulation of digestive system process / positive regulation of corticosterone secretion / regulation of adenylate cyclase activity involved in G protein-coupled receptor signaling pathway / 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 / regulation of serotonin secretion / corticotrophin-releasing factor receptor activity / corticotropin-releasing hormone receptor 2 binding / corticotropin secretion / general adaptation syndrome, behavioral process / positive regulation of corticotropin secretion / positive regulation of cortisol secretion / negative regulation of glucagon secretion / cellular response to corticotropin-releasing hormone stimulus / MECP2 regulates transcription of neuronal ligands / negative regulation of luteinizing hormone secretion / positive regulation of behavioral fear response / glucocorticoid biosynthetic process / negative regulation of norepinephrine secretion / hormone-mediated apoptotic signaling pathway / parturition / monoatomic ion homeostasis / negative regulation of epinephrine secretion / varicosity / negative regulation of voltage-gated calcium channel activity / behavioral response to ethanol / response to ether / corticotropin-releasing hormone receptor 1 binding / neuropeptide hormone activity / fear response / G protein-coupled peptide receptor activity / synaptic transmission, dopaminergic / negative regulation of systemic arterial blood pressure / Class B/2 (Secretin family receptors) / cellular response to cocaine / diterpenoid metabolic process / exploration behavior / response to pain / hypothalamus development / adrenal gland development / response to aldosterone / response to corticosterone / locomotory exploration behavior / positive regulation of calcium ion import / positive regulation of insulin secretion involved in cellular response to glucose stimulus / regulation of NMDA receptor activity / PKA activation in glucagon signalling / associative learning / hair follicle placode formation / intracellular transport / response to immobilization stress / D1 dopamine receptor binding / developmental growth / Hedgehog 'off' state / positive regulation of cAMP-mediated signaling / adenylate cyclase-activating adrenergic receptor signaling pathway / activation of adenylate cyclase activity / adenylate cyclase activator activity / cellular response to dexamethasone stimulus / trans-Golgi network membrane / long-term synaptic potentiation / female pregnancy / lung development / G-protein beta/gamma-subunit complex binding / Olfactory Signaling Pathway / Activation of the phototransduction cascade / G beta:gamma signalling through PLC beta / Presynaptic function of Kainate receptors / Thromboxane signalling through TP receptor / bone development / 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 / Prostacyclin signalling through prostacyclin receptor / Glucagon signaling in metabolic regulation / G beta:gamma signalling through CDC42 / adenylate cyclase-activating G protein-coupled receptor signaling pathway / hormone activity / ADP signalling through P2Y purinoceptor 12 / G beta:gamma signalling through BTK / Sensory perception of sweet, bitter, and umami (glutamate) taste / Synthesis, secretion, and inactivation of Glucagon-like Peptide-1 (GLP-1) / photoreceptor disc membrane / Adrenaline,noradrenaline inhibits insulin secretion / platelet aggregation / cognition / Glucagon-type ligand receptors / Vasopressin regulates renal water homeostasis via Aquaporins / positive regulation of GTPase activity / G alpha (z) signalling events / cellular response to catecholamine stimulus / Glucagon-like Peptide-1 (GLP1) regulates insulin secretion / ADORA2B mediated anti-inflammatory cytokines production / adenylate cyclase-activating dopamine receptor signaling pathway / ADP signalling through P2Y purinoceptor 1 / G beta:gamma signalling through PI3Kgamma 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
| ||||||||||||||||||
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 |
|
-Structure visualization
Movie |
Movie viewer |
---|---|
Structure viewer | Molecule: MolmilJmol/JSmol |
-Downloads & links
-Download
PDBx/mmCIF format | 6p9x.cif.gz | 197.6 KB | Display | PDBx/mmCIF format |
---|---|---|---|---|
PDB format | pdb6p9x.ent.gz | 156 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 |
---|
-Related structure data
Related structure data | 20277MC 0993C 6p9yC M: map data used to model this data C: citing same article (ref.) |
---|---|
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 |
|
---|---|
1 |
|
-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 |
---|---|
#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) |
---|---|
#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 / |
-Experimental details
-Experiment
Experiment | Method: ELECTRON MICROSCOPY |
---|---|
EM experiment | Aggregation state: PARTICLE / 3D reconstruction method: single particle reconstruction |
-Sample preparation
Component |
| ||||||||||||||||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Molecular weight | Experimental value: NO | ||||||||||||||||||||||||||||||
Source (natural) |
| ||||||||||||||||||||||||||||||
Source (recombinant) |
| ||||||||||||||||||||||||||||||
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 |
---|---|
Microscopy | Model: FEI TITAN KRIOS |
Electron gun | Electron source: FIELD EMISSION GUN / Accelerating voltage: 300 kV / Illumination mode: SPOT SCAN |
Electron lens | Mode: BRIGHT FIELDBright-field microscopy / 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 | ||||||||||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
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 |
|