+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-20278 | ||||||||||||||||||||||||||||||
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Title | PAC1 GPCR Receptor complex | ||||||||||||||||||||||||||||||
Map data | post-processed map | ||||||||||||||||||||||||||||||
Sample |
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Function / homology | Function and homology information negative regulation of response to reactive oxygen species / development of primary female sexual characteristics / pituitary adenylate cyclase activating polypeptide activity / vasoactive intestinal polypeptide receptor activity / positive regulation of growth hormone secretion / positive regulation of chemokine (C-C motif) ligand 5 production / positive regulation of cAMP-mediated signaling / NGF-independant TRKA activation / regulation of G protein-coupled receptor signaling pathway / neuropeptide hormone activity ...negative regulation of response to reactive oxygen species / development of primary female sexual characteristics / pituitary adenylate cyclase activating polypeptide activity / vasoactive intestinal polypeptide receptor activity / positive regulation of growth hormone secretion / positive regulation of chemokine (C-C motif) ligand 5 production / positive regulation of cAMP-mediated signaling / NGF-independant TRKA activation / regulation of G protein-coupled receptor signaling pathway / neuropeptide hormone activity / G protein-coupled peptide receptor activity / neuropeptide binding / positive regulation of small GTPase mediated signal transduction / insulin secretion / positive regulation of inositol phosphate biosynthetic process / peptide hormone receptor binding / positive regulation of calcium ion transport into cytosol / peptide hormone binding / PKA activation in glucagon signalling / hair follicle placode formation / adenylate cyclase binding / negative regulation of cell cycle / neuropeptide signaling pathway / developmental growth / D1 dopamine receptor binding / intracellular transport / bicellular tight junction / positive regulation of protein kinase activity / Hedgehog 'off' state / multicellular organismal response to stress / adenylate cyclase-activating adrenergic receptor signaling pathway / activation of adenylate cyclase activity / adenylate cyclase activator activity / cAMP-mediated signaling / positive regulation of GTPase activity / trans-Golgi network membrane / caveola / female pregnancy / 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 / ADP signalling through P2Y purinoceptor 12 / G beta:gamma signalling through BTK / small GTPase binding / 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 / 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 / regulation of protein localization / G-protein beta-subunit binding / Inactivation, recovery and regulation of the phototransduction cascade / heterotrimeric G-protein complex / neuron projection development / G alpha (12/13) signalling events / extracellular vesicle / sensory perception of smell / signaling receptor complex adaptor activity / Thrombin signalling through proteinase activated receptors (PARs) / GTPase binding / response to estradiol / cell-cell signaling / retina development in camera-type eye / Ca2+ pathway / signaling receptor activity / positive regulation of cold-induced thermogenesis / phospholipase C-activating G protein-coupled receptor signaling pathway / positive regulation of cytosolic calcium ion concentration / G alpha (i) signalling events / fibroblast proliferation / G alpha (s) signalling events / spermatogenesis / G alpha (q) signalling events Similarity search - Function | ||||||||||||||||||||||||||||||
Biological species | Homo sapiens (human) / Lama glama (llama) | ||||||||||||||||||||||||||||||
Method | single particle reconstruction / cryo EM / Resolution: 3.01 Å | ||||||||||||||||||||||||||||||
Authors | Belousoff MJ / Liang YL / Sexton P / Danev R | ||||||||||||||||||||||||||||||
Funding support | Australia, Japan, 9 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_20278.map.gz | 8.1 MB | EMDB map data format | |
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Header (meta data) | emd-20278-v30.xml emd-20278.xml | 26.9 KB 26.9 KB | Display Display | EMDB header |
FSC (resolution estimation) | emd_20278_fsc.xml | 10.3 KB | Display | FSC data file |
Images | emd_20278.png | 40.6 KB | ||
Masks | emd_20278_msk_1.map | 91.1 MB | Mask map | |
Others | emd_20278_additional.map.gz emd_20278_half_map_1.map.gz emd_20278_half_map_2.map.gz | 59.2 MB 71.3 MB 71.3 MB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-20278 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-20278 | HTTPS FTP |
-Validation report
Summary document | emd_20278_validation.pdf.gz | 622.5 KB | Display | EMDB validaton report |
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Full document | emd_20278_full_validation.pdf.gz | 622.1 KB | Display | |
Data in XML | emd_20278_validation.xml.gz | 17.5 KB | Display | |
Data in CIF | emd_20278_validation.cif.gz | 22.8 KB | Display | |
Arichive directory | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-20278 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-20278 | HTTPS FTP |
-Related structure data
Related structure data | 6p9yMC 0993C 6p9xC M: atomic model generated by this map C: citing same article (ref.) |
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Similar structure data | |
EM raw data | EMPIAR-10359 (Title: Cryo-EM of PAC1 receptor bound to PACAP38 and Gs protein Data size: 4.8 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_20278.map.gz / Format: CCP4 / Size: 91.1 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Annotation | post-processed map | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Voxel size | X=Y=Z: 0.826 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_20278_msk_1.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Additional map: local resolution filtered map
File | emd_20278_additional.map | ||||||||||||
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Annotation | local resolution filtered map | ||||||||||||
Projections & Slices |
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Density Histograms |
-Half map: half-map 2
File | emd_20278_half_map_1.map | ||||||||||||
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Annotation | half-map 2 | ||||||||||||
Projections & Slices |
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Density Histograms |
-Half map: half-map 1
File | emd_20278_half_map_2.map | ||||||||||||
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Annotation | half-map 1 | ||||||||||||
Projections & Slices |
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Density Histograms |
-Sample components
+Entire : Complex of active-state Pituitary adenylate cyclase-activating po...
+Supramolecule #1: Complex of active-state Pituitary adenylate cyclase-activating po...
+Supramolecule #2: Guanine nucleotide-binding protein G(s) subunit alpha isoforms sh...
+Supramolecule #3: Nanobody 35
+Supramolecule #4: Pituitary adenylate cyclase-activating polypeptide type I receptor
+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: Pituitary adenylate cyclase-activating polypeptide
+Macromolecule #6: Pituitary adenylate cyclase-activating polypeptide type I receptor
-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: 1.03 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 |