+Open data
-Basic information
Entry | Database: PDB / ID: 6wzg | |||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Title | Human secretin receptor Gs complex | |||||||||||||||
Components |
| |||||||||||||||
Keywords | MEMBRANE PROTEIN / GPCR / Gs coupled / Complex | |||||||||||||||
Function / homology | Function and homology information secretin receptor activity / digestive hormone activity / positive regulation of somatostatin secretion / negative regulation of gastrin-induced gastric acid secretion / positive regulation of pancreatic juice secretion / regulation of appetite / pancreatic juice secretion / intracellular water homeostasis / positive regulation of lipid catabolic process / positive regulation of cAMP-mediated signaling ...secretin receptor activity / digestive hormone activity / positive regulation of somatostatin secretion / negative regulation of gastrin-induced gastric acid secretion / positive regulation of pancreatic juice secretion / regulation of appetite / pancreatic juice secretion / intracellular water homeostasis / positive regulation of lipid catabolic process / positive regulation of cAMP-mediated signaling / embryonic digestive tract development / G protein-coupled peptide receptor activity / diet induced thermogenesis / cytoplasmic microtubule / peptide hormone binding / PKA activation in glucagon signalling / hair follicle placode formation / mu-type opioid receptor binding / developmental growth / corticotropin-releasing hormone receptor 1 binding / intracellular transport / D1 dopamine receptor binding / Hedgehog 'off' state / beta-2 adrenergic receptor binding / adenylate cyclase-activating adrenergic receptor signaling pathway / activation of adenylate cyclase activity / adenylate cyclase activator activity / response to nutrient levels / trans-Golgi network membrane / G protein-coupled receptor binding / hippocampus development / insulin-like growth factor receptor binding / ionotropic glutamate receptor binding / G-protein beta/gamma-subunit complex binding / regulation of synaptic plasticity / 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 activation / hormone activity / G protein-coupled acetylcholine receptor signaling pathway / brain development / 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 / 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 / platelet aggregation / 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 / G-protein beta-subunit binding / Inactivation, recovery and regulation of the phototransduction cascade / heterotrimeric G-protein complex / 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 / retina development in camera-type eye / phospholipase C-activating G protein-coupled receptor signaling pathway / Ca2+ pathway / positive regulation of cold-induced thermogenesis / G alpha (i) signalling events / fibroblast proliferation / G alpha (s) signalling events / G alpha (q) signalling events / cell population proliferation / Ras protein signal transduction / Extra-nuclear estrogen signaling / cell surface receptor signaling pathway / G protein-coupled receptor signaling pathway / lysosomal membrane / signaling receptor binding / GTPase activity / synapse / protein-containing complex binding Similarity search - Function | |||||||||||||||
Biological species | Homo sapiens (human) Lama glama (llama) | |||||||||||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 2.3 Å | |||||||||||||||
Authors | Piper, S.J. / Belousoff, M.J. / Danev, R. | |||||||||||||||
Funding support | United States, Australia, United Kingdom, 4items
| |||||||||||||||
Citation | Journal: Nat Commun / Year: 2020 Title: Structure and dynamics of the active Gs-coupled human secretin receptor. Authors: Maoqing Dong / Giuseppe Deganutti / Sarah J Piper / Yi-Lynn Liang / Maryam Khoshouei / Matthew J Belousoff / Kaleeckal G Harikumar / Christopher A Reynolds / Alisa Glukhova / Sebastian G B ...Authors: Maoqing Dong / Giuseppe Deganutti / Sarah J Piper / Yi-Lynn Liang / Maryam Khoshouei / Matthew J Belousoff / Kaleeckal G Harikumar / Christopher A Reynolds / Alisa Glukhova / Sebastian G B Furness / Arthur Christopoulos / Radostin Danev / Denise Wootten / Patrick M Sexton / Laurence J Miller / Abstract: The class B secretin GPCR (SecR) has broad physiological effects, with target potential for treatment of metabolic and cardiovascular disease. Molecular understanding of SecR binding and activation ...The class B secretin GPCR (SecR) has broad physiological effects, with target potential for treatment of metabolic and cardiovascular disease. Molecular understanding of SecR binding and activation is important for its therapeutic exploitation. We combined cryo-electron microscopy, molecular dynamics, and biochemical cross-linking to determine a 2.3 Å structure, and interrogate dynamics, of secretin bound to the SecR:Gs complex. SecR exhibited a unique organization of its extracellular domain (ECD) relative to its 7-transmembrane (TM) core, forming more extended interactions than other family members. Numerous polar interactions formed between secretin and the receptor extracellular loops (ECLs) and TM helices. Cysteine-cross-linking, cryo-electron microscopy multivariate analysis and molecular dynamics simulations revealed that interactions between peptide and receptor were dynamic, and suggested a model for initial peptide engagement where early interactions between the far N-terminus of the peptide and SecR ECL2 likely occur following initial binding of the peptide C-terminus to the ECD. | |||||||||||||||
History |
|
-Structure visualization
Movie |
Movie viewer |
---|---|
Structure viewer | Molecule: MolmilJmol/JSmol |
-Downloads & links
-Download
PDBx/mmCIF format | 6wzg.cif.gz | 209.8 KB | Display | PDBx/mmCIF format |
---|---|---|---|---|
PDB format | pdb6wzg.ent.gz | 166.4 KB | Display | PDB format |
PDBx/mmJSON format | 6wzg.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 6wzg_validation.pdf.gz | 940.4 KB | Display | wwPDB validaton report |
---|---|---|---|---|
Full document | 6wzg_full_validation.pdf.gz | 947.3 KB | Display | |
Data in XML | 6wzg_validation.xml.gz | 44.3 KB | Display | |
Data in CIF | 6wzg_validation.cif.gz | 67.9 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/wz/6wzg ftp://data.pdbj.org/pub/pdb/validation_reports/wz/6wzg | HTTPS FTP |
-Related structure data
Related structure data | 21972MC 6wi9C C: citing same article (ref.) M: map data used to model this data |
---|---|
Similar structure data |
-Links
-Assembly
Deposited unit |
|
---|---|
1 |
|
-Components
-Guanine nucleotide-binding protein ... , 3 types, 3 molecules ABG
#3: Protein | Mass: 45699.434 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 |
---|---|
#4: Protein | Mass: 37416.930 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 |
#5: 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 |
-Protein/peptide / Protein / Antibody , 3 types, 3 molecules PRN
#1: Protein/peptide | Mass: 3045.436 Da / Num. of mol.: 1 / Source method: obtained synthetically / Source: (synth.) Homo sapiens (human) / References: UniProt: P09683 |
---|---|
#2: Protein | Mass: 51928.855 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: SCTR / Production host: Trichoplusia ni (cabbage looper) / References: UniProt: P47872 |
#6: 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) |
-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 | Conc.: 8.1 mg/ml / Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES | ||||||||||||||||||||||||||||||
Specimen support | Grid material: GOLD | ||||||||||||||||||||||||||||||
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: FLOOD BEAM |
Electron lens | Mode: BRIGHT FIELD |
Image recording | Electron dose: 52.9 e/Å2 / Detector mode: COUNTING / Film or detector model: GATAN K3 BIOQUANTUM (6k x 4k) |
-Processing
CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION |
---|---|
Symmetry | Point symmetry: C1 (asymmetric) |
3D reconstruction | Resolution: 2.3 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 349811 / Symmetry type: POINT |