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Yorodumi- EMDB-30590: Cryo-EM structure of the human glucagon-like peptide-2 receptor-G... -
+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-30590 | |||||||||
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Title | Cryo-EM structure of the human glucagon-like peptide-2 receptor-Gs protein complex | |||||||||
Map data | ||||||||||
Sample |
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Function / homology | Function and homology information glucagon receptor binding / Olfactory Signaling Pathway / Sensory perception of sweet, bitter, and umami (glutamate) taste / Synthesis, secretion, and inactivation of Glucagon-like Peptide-1 (GLP-1) / glucagon receptor activity / sensory perception of chemical stimulus / mu-type opioid receptor binding / Activation of the phototransduction cascade / corticotropin-releasing hormone receptor 1 binding / D1 dopamine receptor binding ...glucagon receptor binding / Olfactory Signaling Pathway / Sensory perception of sweet, bitter, and umami (glutamate) taste / Synthesis, secretion, and inactivation of Glucagon-like Peptide-1 (GLP-1) / glucagon receptor activity / sensory perception of chemical stimulus / mu-type opioid receptor binding / Activation of the phototransduction cascade / corticotropin-releasing hormone receptor 1 binding / D1 dopamine receptor binding / negative regulation of execution phase of apoptosis / G protein-coupled peptide receptor activity / feeding behavior / Activation of G protein gated Potassium channels / G-protein activation / G beta:gamma signalling through PI3Kgamma / Prostacyclin signalling through prostacyclin receptor / G beta:gamma signalling through PLC beta / ADP signalling through P2Y purinoceptor 1 / Thromboxane signalling through TP receptor / Presynaptic function of Kainate receptors / G beta:gamma signalling through CDC42 / Inhibition of voltage gated Ca2+ channels via Gbeta/gamma subunits / Glucagon-type ligand receptors / G alpha (12/13) signalling events / G beta:gamma signalling through BTK / ADP signalling through P2Y purinoceptor 12 / Adrenaline,noradrenaline inhibits insulin secretion / Cooperation of PDCL (PhLP1) and TRiC/CCT in G-protein beta folding / Thrombin signalling through proteinase activated receptors (PARs) / Ca2+ pathway / beta-2 adrenergic receptor binding / Extra-nuclear estrogen signaling / G alpha (z) signalling events / G alpha (s) signalling events / G alpha (q) signalling events / G alpha (i) signalling events / Glucagon-like Peptide-1 (GLP1) regulates insulin secretion / Vasopressin regulates renal water homeostasis via Aquaporins / positive regulation of calcium ion import / cellular response to glucagon stimulus / adenylate cyclase-activating adrenergic receptor signaling pathway / adenylate cyclase activator activity / positive regulation of insulin secretion involved in cellular response to glucose stimulus / regulation of insulin secretion / peptide hormone binding / Synthesis, secretion, and deacylation of Ghrelin / negative regulation of inflammatory response to antigenic stimulus / positive regulation of gluconeogenesis / insulin-like growth factor receptor binding / ionotropic glutamate receptor binding / protein kinase A signaling / G-protein beta/gamma-subunit complex binding / positive regulation of peptidyl-threonine phosphorylation / response to activity / gluconeogenesis / G protein-coupled receptor activity / adenylate cyclase-activating G protein-coupled receptor signaling pathway / membrane => GO:0016020 / adenylate cyclase-modulating G protein-coupled receptor signaling pathway / hormone activity / Glucagon signaling in metabolic regulation / Synthesis, secretion, and inactivation of Glucagon-like Peptide-1 (GLP-1) / Glucagon-type ligand receptors / photoreceptor disc membrane / Glucagon-like Peptide-1 (GLP1) regulates insulin secretion / ADORA2B mediated anti-inflammatory cytokines production / cellular response to catecholamine stimulus / adenylate cyclase-activating dopamine receptor signaling pathway / cellular response to prostaglandin E stimulus / G-protein beta-subunit binding / heterotrimeric G-protein complex / signaling receptor complex adaptor activity / positive regulation of peptidyl-serine phosphorylation / glucose homeostasis / G alpha (s) signalling events / G alpha (q) signalling events / secretory granule lumen / positive regulation of ERK1 and ERK2 cascade / cell surface receptor signaling pathway / G protein-coupled receptor signaling pathway / endoplasmic reticulum lumen / signaling receptor binding / GTPase activity / positive regulation of cell population proliferation / GTP binding / negative regulation of apoptotic process / extracellular space / extracellular region / identical protein binding / membrane / metal ion binding / plasma membrane / cytoplasm Similarity search - Function | |||||||||
Biological species | Bos taurus (cattle) / synthetic construct (others) / Homo sapiens (human) | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 3.0 Å | |||||||||
Authors | Sun W / Chen L / Zhou Q / Zhao L / Zhang H / Cong Z / Shen D / Zhao F / Zhou F / Cai X ...Sun W / Chen L / Zhou Q / Zhao L / Zhang H / Cong Z / Shen D / Zhao F / Zhou F / Cai X / Chen Y / Zhou Y / Gadgaard S / van der Velden WJ / Zhao S / Jiang Y / Rosenkilde MM / Yang D / Xu HE / Zhang Y / Wang M | |||||||||
Citation | Journal: Cell Res / Year: 2020 Title: A unique hormonal recognition feature of the human glucagon-like peptide-2 receptor. Authors: Wen Sun / Li-Nan Chen / Qingtong Zhou / Li-Hua Zhao / Dehua Yang / Huibing Zhang / Zhaotong Cong / Dan-Dan Shen / Fenghui Zhao / Fulai Zhou / Xiaoqing Cai / Yan Chen / Yan Zhou / Sarina ...Authors: Wen Sun / Li-Nan Chen / Qingtong Zhou / Li-Hua Zhao / Dehua Yang / Huibing Zhang / Zhaotong Cong / Dan-Dan Shen / Fenghui Zhao / Fulai Zhou / Xiaoqing Cai / Yan Chen / Yan Zhou / Sarina Gadgaard / Wijnand J C van der Velden / Suwen Zhao / Yi Jiang / Mette M Rosenkilde / H Eric Xu / Yan Zhang / Ming-Wei Wang / Abstract: Glucagon-like peptides (GLP-1 and GLP-2) are two proglucagon-derived intestinal hormones that mediate distinct physiological functions through two related receptors (GLP-1R and GLP-2R) which are ...Glucagon-like peptides (GLP-1 and GLP-2) are two proglucagon-derived intestinal hormones that mediate distinct physiological functions through two related receptors (GLP-1R and GLP-2R) which are important drug targets for metabolic disorders and Crohn's disease, respectively. Despite great progress in GLP-1R structure determination, our understanding on the differences of peptide binding and signal transduction between these two receptors remains elusive. Here we report the electron microscopy structure of the human GLP-2R in complex with GLP-2 and a G heterotrimer. To accommodate GLP-2 rather than GLP-1, GLP-2R fine-tunes the conformations of the extracellular parts of transmembrane helices (TMs) 1, 5, 7 and extracellular loop 1 (ECL1). In contrast to GLP-1, the N-terminal histidine of GLP-2 penetrates into the receptor core with a unique orientation. The middle region of GLP-2 engages with TM1 and TM7 more extensively than with ECL2, and the GLP-2 C-terminus closely attaches to ECL1, which is the most protruded among 9 class B G protein-coupled receptors (GPCRs). Functional studies revealed that the above three segments of GLP-2 are essential for GLP-2 recognition and receptor activation, especially the middle region. These results provide new insights into the molecular basis of ligand specificity in class B GPCRs and may facilitate the development of more specific therapeutics. | |||||||||
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_30590.map.gz | 28.5 MB | EMDB map data format | |
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Header (meta data) | emd-30590-v30.xml emd-30590.xml | 18.9 KB 18.9 KB | Display Display | EMDB header |
Images | emd_30590.png | 64.2 KB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-30590 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-30590 | HTTPS FTP |
-Validation report
Summary document | emd_30590_validation.pdf.gz | 356.1 KB | Display | EMDB validaton report |
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Full document | emd_30590_full_validation.pdf.gz | 355.7 KB | Display | |
Data in XML | emd_30590_validation.xml.gz | 5.9 KB | Display | |
Data in CIF | emd_30590_validation.cif.gz | 6.7 KB | Display | |
Arichive directory | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-30590 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-30590 | HTTPS FTP |
-Related structure data
Related structure data | 7d68MC M: atomic model generated by this map C: citing same article (ref.) |
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Similar structure data |
-Links
EMDB pages | EMDB (EBI/PDBe) / EMDataResource |
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Related items in Molecule of the Month |
-Map
File | Download / File: emd_30590.map.gz / Format: CCP4 / Size: 42.9 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Projections & slices | Image control
Images are generated by Spider. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Voxel size | X=Y=Z: 1.014 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Details | EMDB XML:
CCP4 map header:
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-Supplemental data
-Sample components
+Entire : Cryo-EM structure of the human glucagon-like peptide-2 receptor-G...
+Supramolecule #1: Cryo-EM structure of the human glucagon-like peptide-2 receptor-G...
+Supramolecule #2: Guanine nucleotide-binding protein
+Supramolecule #3: Nanobody-35
+Supramolecule #4: Glucagon-like peptide 2 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: Pro-glucagon
+Macromolecule #6: Glucagon-like peptide 2 receptor
+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 K2 QUANTUM (4k x 4k) / Detector mode: COUNTING / Average electron dose: 64.0 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD |
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |
-Image processing
Startup model | Type of model: EMDB MAP EMDB ID: |
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Final reconstruction | Resolution.type: BY AUTHOR / Resolution: 3.0 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 284669 |
Initial angle assignment | Type: RANDOM ASSIGNMENT |
Final angle assignment | Type: MAXIMUM LIKELIHOOD |