+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-20277 | ||||||||||||||||||
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Title | CRF1 Receptor Gs GPCR protein complex with CRF1 peptide | ||||||||||||||||||
Map data | Post-processed map | ||||||||||||||||||
Sample |
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Function / homology | Function and homology information corticotropin-releasing hormone activity / positive regulation of digestive system process / positive regulation of corticosterone secretion / diterpenoid metabolic process / 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 / corticotrophin-releasing factor receptor activity ...corticotropin-releasing hormone activity / positive regulation of digestive system process / positive regulation of corticosterone secretion / diterpenoid metabolic process / 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 / corticotrophin-releasing factor receptor activity / corticotropin-releasing hormone receptor 2 binding / corticotropin secretion / positive regulation of corticotropin secretion / positive regulation of cortisol secretion / regulation of serotonin secretion / negative regulation of glucagon secretion / general adaptation syndrome, behavioral process / MECP2 regulates transcription of neuronal ligands / cellular response to corticotropin-releasing hormone stimulus / positive regulation of behavioral fear response / glucocorticoid biosynthetic process / negative regulation of norepinephrine secretion / parturition / hormone-mediated apoptotic signaling pathway / negative regulation of luteinizing hormone secretion / negative regulation of epinephrine secretion / monoatomic ion homeostasis / varicosity / negative regulation of voltage-gated calcium channel activity / behavioral response to ethanol / positive regulation of cAMP-mediated signaling / response to ether / corticotropin-releasing hormone receptor 1 binding / neuropeptide hormone activity / fear response / 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 / exploration behavior / adrenal gland development / hypothalamus development / response to aldosterone / response to corticosterone / response to pain / positive regulation of calcium ion import / locomotory exploration behavior / positive regulation of insulin secretion involved in cellular response to glucose stimulus / associative learning / PKA activation in glucagon signalling / hair follicle placode formation / response to immobilization stress / developmental growth / D1 dopamine receptor binding / intracellular transport / Hedgehog 'off' state / cellular response to dexamethasone stimulus / adenylate cyclase-activating adrenergic receptor signaling pathway / activation of adenylate cyclase activity / adenylate cyclase activator activity / lung development / trans-Golgi network membrane / female pregnancy / long-term synaptic potentiation / G-protein beta/gamma-subunit complex binding / bone development / 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 / adenylate cyclase-activating G protein-coupled receptor signaling pathway / G protein-coupled acetylcholine receptor signaling pathway / G-protein activation / hormone activity / 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 / 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 / response to estrogen / ADORA2B mediated anti-inflammatory cytokines production / sensory perception of taste / ADP signalling through P2Y purinoceptor 1 / adenylate cyclase-activating dopamine receptor signaling pathway Similarity search - Function | ||||||||||||||||||
Biological species | Homo sapiens (human) / Lama glama (llama) | ||||||||||||||||||
Method | single particle reconstruction / cryo EM / Resolution: 2.91 Å | ||||||||||||||||||
Authors | Belousoff MJ / Liang YL / Sexton P / Danev R | ||||||||||||||||||
Funding support | Australia, Japan, 5 items
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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 | EM map: SurfViewMolmilJmol/JSmol |
Supplemental images |
-Downloads & links
-EMDB archive
Map data | emd_20277.map.gz | 19.4 MB | EMDB map data format | |
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Header (meta data) | emd-20277-v30.xml emd-20277.xml | 26.2 KB 26.2 KB | Display Display | EMDB header |
FSC (resolution estimation) | emd_20277_fsc.xml | 6.3 KB | Display | FSC data file |
Images | emd_20277.png | 49.2 KB | ||
Masks | emd_20277_msk_1.map | 20.8 MB | Mask map | |
Others | emd_20277_additional.map.gz emd_20277_half_map_1.map.gz emd_20277_half_map_2.map.gz | 14 MB 15.8 MB 15.8 MB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-20277 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-20277 | HTTPS FTP |
-Validation report
Summary document | emd_20277_validation.pdf.gz | 686.4 KB | Display | EMDB validaton report |
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Full document | emd_20277_full_validation.pdf.gz | 686 KB | Display | |
Data in XML | emd_20277_validation.xml.gz | 11.8 KB | Display | |
Data in CIF | emd_20277_validation.cif.gz | 16.2 KB | Display | |
Arichive directory | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-20277 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-20277 | HTTPS FTP |
-Related structure data
Related structure data | 6p9xMC 0993C 6p9yC M: atomic model generated by this map 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
EMDB pages | EMDB (EBI/PDBe) / EMDataResource |
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Related items in Molecule of the Month |
-Map
File | Download / File: emd_20277.map.gz / Format: CCP4 / Size: 20.8 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Annotation | Post-processed map | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Voxel size | X=Y=Z: 1.20727 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Details | EMDB XML:
CCP4 map header:
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-Supplemental data
-Mask #1
File | emd_20277_msk_1.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Additional map: additional map
File | emd_20277_additional.map | ||||||||||||
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Annotation | additional map | ||||||||||||
Projections & Slices |
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Density Histograms |
-Half map: half map - even
File | emd_20277_half_map_1.map | ||||||||||||
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Annotation | half map - even | ||||||||||||
Projections & Slices |
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Density Histograms |
-Half map: half map - odd
File | emd_20277_half_map_2.map | ||||||||||||
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Annotation | half map - odd | ||||||||||||
Projections & Slices |
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Density Histograms |
-Sample components
+Entire : Complex of active-state Corticotropin-releasing hormone receptor ...
+Supramolecule #1: Complex of active-state Corticotropin-releasing hormone receptor ...
+Supramolecule #2: Guanine nucleotide-binding protein G(s) subunit alpha isoforms sh...
+Supramolecule #3: Nanobody 35
+Supramolecule #4: Corticoliberin
+Macromolecule #1: Guanine nucleotide-binding protein G(s) subunit alpha isoforms short
+Macromolecule #2: Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1
+Macromolecule #3: Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2
+Macromolecule #4: Nanobody 35
+Macromolecule #5: Corticotropin-releasing factor receptor 1
+Macromolecule #6: Corticoliberin
+Macromolecule #7: water
-Experimental details
-Structure determination
Method | cryo EM |
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Processing | single particle reconstruction |
Aggregation state | particle |
-Sample preparation
Buffer | pH: 7.4 |
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Vitrification | Cryogen name: ETHANE |
-Electron microscopy
Microscope | FEI TITAN KRIOS |
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Image recording | Film or detector model: GATAN K3 (6k x 4k) / Number grids imaged: 1 / Average exposure time: 3.7 sec. / Average electron dose: 1.0 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN |
Electron optics | Illumination mode: SPOT SCAN / Imaging mode: BRIGHT FIELD / Cs: 2.7 mm |
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |