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- PDB-6lml: Cryo-EM structure of the human glucagon receptor in complex with Gi1 -
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Open data
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Basic information
Entry | Database: PDB / ID: 6lml | |||||||||||||||||||||||||||
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Title | Cryo-EM structure of the human glucagon receptor in complex with Gi1 | |||||||||||||||||||||||||||
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![]() | SIGNALING PROTEIN / glucagon receptor / GPCR / Gi1 protein | |||||||||||||||||||||||||||
Function / homology | ![]() glucagon receptor binding / regulation of glycogen metabolic process / glucagon receptor activity / negative regulation of execution phase of apoptosis / feeding behavior / positive regulation of calcium ion import / cellular response to glucagon stimulus / response to starvation / exocytosis / positive regulation of insulin secretion involved in cellular response to glucose stimulus ...glucagon receptor binding / regulation of glycogen metabolic process / glucagon receptor activity / negative regulation of execution phase of apoptosis / feeding behavior / positive regulation of calcium ion import / cellular response to glucagon stimulus / response to starvation / exocytosis / positive regulation of insulin secretion involved in cellular response to glucose stimulus / peptide hormone binding / regulation of insulin secretion / Synthesis, secretion, and deacylation of Ghrelin / Adenylate cyclase inhibitory pathway / positive regulation of protein localization to cell cortex / generation of precursor metabolites and energy / hormone-mediated signaling pathway / regulation of cAMP-mediated signaling / D2 dopamine receptor binding / G protein-coupled serotonin receptor binding / response to nutrient / regulation of mitotic spindle organization / cellular response to forskolin / positive regulation of gluconeogenesis / protein kinase A signaling / adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway / cellular response to starvation / guanyl-nucleotide exchange factor activity / positive regulation of peptidyl-threonine phosphorylation / response to activity / gluconeogenesis / Regulation of insulin secretion / G protein-coupled receptor binding / regulation of blood pressure / G-protein beta/gamma-subunit complex binding / 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 / hormone activity / 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 / response to peptide hormone / 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 / 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 / GDP binding / G-protein beta-subunit binding / Inactivation, recovery and regulation of the phototransduction cascade / heterotrimeric G-protein complex / positive regulation of peptidyl-serine phosphorylation / G alpha (12/13) signalling events / extracellular vesicle / glucose homeostasis / signaling receptor complex adaptor activity / Thrombin signalling through proteinase activated receptors (PARs) / GTPase binding / retina development in camera-type eye / Ca2+ pathway / phospholipase C-activating G protein-coupled receptor signaling pathway / cell cortex / midbody / G alpha (i) signalling events / fibroblast proliferation / G alpha (s) signalling events / Ras protein signal transduction / G alpha (q) signalling events / secretory granule lumen / Extra-nuclear estrogen signaling / cell population proliferation / positive regulation of ERK1 and ERK2 cascade / endosome / cell surface receptor signaling pathway / G protein-coupled receptor signaling pathway / cell division / endoplasmic reticulum lumen Similarity search - Function | |||||||||||||||||||||||||||
Biological species | ![]() ![]() ![]() | |||||||||||||||||||||||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.9 Å | |||||||||||||||||||||||||||
![]() | Qiao, A. / Han, S. / Li, X. / Sun, F. / Zhao, Q. / Wu, B. | |||||||||||||||||||||||||||
Funding support | ![]()
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![]() | ![]() Title: Structural basis of G and G recognition by the human glucagon receptor. Authors: Anna Qiao / Shuo Han / Xinmei Li / Zhixin Li / Peishen Zhao / Antao Dai / Rulve Chang / Linhua Tai / Qiuxiang Tan / Xiaojing Chu / Limin Ma / Thor Seneca Thorsen / Steffen Reedtz-Runge / ...Authors: Anna Qiao / Shuo Han / Xinmei Li / Zhixin Li / Peishen Zhao / Antao Dai / Rulve Chang / Linhua Tai / Qiuxiang Tan / Xiaojing Chu / Limin Ma / Thor Seneca Thorsen / Steffen Reedtz-Runge / Dehua Yang / Ming-Wei Wang / Patrick M Sexton / Denise Wootten / Fei Sun / Qiang Zhao / Beili Wu / ![]() ![]() ![]() Abstract: Class B G protein-coupled receptors, an important class of therapeutic targets, signal mainly through the G class of heterotrimeric G proteins, although they do display some promiscuity in G protein ...Class B G protein-coupled receptors, an important class of therapeutic targets, signal mainly through the G class of heterotrimeric G proteins, although they do display some promiscuity in G protein binding. Using cryo-electron microscopy, we determined the structures of the human glucagon receptor (GCGR) bound to glucagon and distinct classes of heterotrimeric G proteins, G or G These two structures adopt a similar open binding cavity to accommodate G and G The G binding selectivity of GCGR is explained by a larger interaction interface, but there are specific interactions that affect G more than G binding. Conformational differences in the receptor intracellular loops were found to be key selectivity determinants. These distinctions in transducer engagement were supported by mutagenesis and functional studies. | |||||||||||||||||||||||||||
History |
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Structure visualization
Movie |
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Structure viewer | Molecule: ![]() ![]() |
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Downloads & links
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Download
PDBx/mmCIF format | ![]() | 226.4 KB | Display | ![]() |
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PDB format | ![]() | 177.9 KB | Display | ![]() |
PDBx/mmJSON format | ![]() | Tree view | ![]() | |
Others | ![]() |
-Validation report
Arichive directory | ![]() ![]() | HTTPS FTP |
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-Related structure data
Related structure data | ![]() 0918MC ![]() 0917C ![]() 6lmkC M: map data used to model this data C: citing same article ( |
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Similar structure data |
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Links
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Assembly
Deposited unit | ![]()
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Components
-Guanine nucleotide-binding protein ... , 3 types, 3 molecules ABC
#1: Protein | Mass: 40414.047 Da / Num. of mol.: 1 / Mutation: S47N,G203A,E245A,A326S Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() |
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#2: Protein | Mass: 38744.371 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() |
#3: Protein | Mass: 7861.143 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() |
-Antibody / Protein/peptide / Protein , 3 types, 3 molecules DER
#4: Antibody | Mass: 26337.307 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() |
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#5: Protein/peptide | Mass: 3486.781 Da / Num. of mol.: 1 / Source method: obtained synthetically / Source: (synth.) ![]() |
#6: Protein | Mass: 48571.410 Da / Num. of mol.: 1 / Mutation: E126R,T200W,A366M Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() |
-Experimental details
-Experiment
Experiment | Method: ELECTRON MICROSCOPY |
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EM experiment | Aggregation state: PARTICLE / 3D reconstruction method: single particle reconstruction |
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Sample preparation
Component | Name: Complex of glucagon receptor bound to glucagon, Gi1 protein and antibody Type: COMPLEX / Entity ID: all / Source: RECOMBINANT |
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Source (natural) | Organism: ![]() |
Source (recombinant) | Organism: ![]() |
Buffer solution | pH: 7.5 |
Specimen | Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES |
Vitrification | Cryogen name: ETHANE |
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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: ![]() |
Electron lens | Mode: BRIGHT FIELD |
Image recording | Electron dose: 1.875 e/Å2 / Film or detector model: GATAN K2 SUMMIT (4k x 4k) |
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Processing
CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION | ||||||||||||||||||||||||
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Symmetry | Point symmetry: C1 (asymmetric) | ||||||||||||||||||||||||
3D reconstruction | Resolution: 3.9 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 312974 / Symmetry type: POINT | ||||||||||||||||||||||||
Refinement | Stereochemistry target values: GeoStd + Monomer Library + CDL v1.2 | ||||||||||||||||||||||||
Displacement parameters | Biso mean: 75.59 Å2 | ||||||||||||||||||||||||
Refine LS restraints |
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