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Yorodumi- EMDB-21992: GLP-1 peptide hormone bound to Glucagon-Like peptide-1 (GLP-1) Re... -
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Open data
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Basic information
| Entry | Database: EMDB / ID: EMD-21992 | ||||||||||||||||||
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| Title | GLP-1 peptide hormone bound to Glucagon-Like peptide-1 (GLP-1) Receptor | ||||||||||||||||||
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Keywords | G-coupled protein receptor / GPCR / MEMBRANE PROTEIN | ||||||||||||||||||
| Function / homology | Function and homology informationglucagon receptor binding / glucagon-like peptide 1 receptor activity / glucagon receptor activity / : / positive regulation of blood pressure / hormone secretion / post-translational protein targeting to membrane, translocation / negative regulation of execution phase of apoptosis / feeding behavior / response to psychosocial stress ...glucagon receptor binding / glucagon-like peptide 1 receptor activity / glucagon receptor activity / : / positive regulation of blood pressure / hormone secretion / post-translational protein targeting to membrane, translocation / negative regulation of execution phase of apoptosis / feeding behavior / response to psychosocial stress / regulation of heart contraction / positive regulation of calcium ion import / peptide hormone binding / PKA activation in glucagon signalling / Synthesis, secretion, and deacylation of Ghrelin / developmental growth / hair follicle placode formation / D1 dopamine receptor binding / positive regulation of insulin secretion involved in cellular response to glucose stimulus / intracellular transport / vascular endothelial cell response to laminar fluid shear stress / renal water homeostasis / activation of adenylate cyclase activity / Hedgehog 'off' state / negative regulation of blood pressure / adenylate cyclase-activating adrenergic receptor signaling pathway / positive regulation of gluconeogenesis / cellular response to glucagon stimulus / regulation of insulin secretion / adenylate cyclase activator activity / trans-Golgi network membrane / response to activity / gluconeogenesis / negative regulation of inflammatory response to antigenic stimulus / hormone activity / bone development / adenylate cyclase-modulating G protein-coupled receptor signaling pathway / platelet aggregation / G-protein beta/gamma-subunit complex binding / cognition / 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 / G protein-coupled acetylcholine receptor signaling pathway / adenylate cyclase-activating G protein-coupled receptor signaling pathway / Activation of G protein gated Potassium channels / Inhibition of voltage gated Ca2+ channels via Gbeta/gamma subunits / G-protein activation / Prostacyclin signalling through prostacyclin receptor / G beta:gamma signalling through CDC42 / Glucagon signaling in metabolic regulation / G beta:gamma signalling through BTK / Synthesis, secretion, and inactivation of Glucagon-like Peptide-1 (GLP-1) / ADP signalling through P2Y purinoceptor 12 / photoreceptor disc membrane / Sensory perception of sweet, bitter, and umami (glutamate) taste / Glucagon-type ligand receptors / Adrenaline,noradrenaline inhibits insulin secretion / Vasopressin regulates renal water homeostasis via Aquaporins / Glucagon-like Peptide-1 (GLP1) regulates insulin secretion / G alpha (z) signalling events / cellular response to catecholamine stimulus / ADP signalling through P2Y purinoceptor 1 / ADORA2B mediated anti-inflammatory cytokines production / G beta:gamma signalling through PI3Kgamma / sensory perception of smell / adenylate cyclase-activating dopamine receptor signaling pathway / Cooperation of PDCL (PhLP1) and TRiC/CCT in G-protein beta folding / transmembrane signaling receptor activity / GPER1 signaling / Inactivation, recovery and regulation of the phototransduction cascade / cellular response to prostaglandin E stimulus / G-protein beta-subunit binding / heterotrimeric G-protein complex / glucose homeostasis / G alpha (12/13) signalling events / sensory perception of taste / extracellular vesicle / signaling receptor complex adaptor activity / Thrombin signalling through proteinase activated receptors (PARs) / positive regulation of cold-induced thermogenesis / retina development in camera-type eye / G protein activity / positive regulation of cytosolic calcium ion concentration / GTPase binding / Ca2+ pathway / fibroblast proliferation / High laminar flow shear stress activates signaling by PIEZO1 and PECAM1:CDH5:KDR in endothelial cells / secretory granule lumen / G alpha (i) signalling events / G alpha (s) signalling events / phospholipase C-activating G protein-coupled receptor signaling pathway / G alpha (q) signalling events / Hydrolases; Acting on acid anhydrides; Acting on GTP to facilitate cellular and subcellular movement / Ras protein signal transduction / learning or memory / Extra-nuclear estrogen signaling / cell surface receptor signaling pathway Similarity search - Function | ||||||||||||||||||
| Biological species | Homo sapiens (human) / ![]() | ||||||||||||||||||
| Method | single particle reconstruction / cryo EM / Resolution: 2.1 Å | ||||||||||||||||||
Authors | Belousoff MJ / Zhang X | ||||||||||||||||||
| Funding support | Australia, 5 items
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Citation | Journal: Mol Cell / Year: 2020Title: Differential GLP-1R Binding and Activation by Peptide and Non-peptide Agonists. Authors: Xin Zhang / Matthew J Belousoff / Peishen Zhao / Albert J Kooistra / Tin T Truong / Sheng Yu Ang / Christina Rye Underwood / Thomas Egebjerg / Petr Šenel / Gregory D Stewart / Yi-Lynn Liang ...Authors: Xin Zhang / Matthew J Belousoff / Peishen Zhao / Albert J Kooistra / Tin T Truong / Sheng Yu Ang / Christina Rye Underwood / Thomas Egebjerg / Petr Šenel / Gregory D Stewart / Yi-Lynn Liang / Alisa Glukhova / Hari Venugopal / Arthur Christopoulos / Sebastian G B Furness / Laurence J Miller / Steffen Reedtz-Runge / Christopher J Langmead / David E Gloriam / Radostin Danev / Patrick M Sexton / Denise Wootten / ![]() Abstract: Peptide drugs targeting class B1 G-protein-coupled receptors (GPCRs) can treat multiple diseases; however, there remains substantial interest in the development of orally delivered non-peptide drugs. ...Peptide drugs targeting class B1 G-protein-coupled receptors (GPCRs) can treat multiple diseases; however, there remains substantial interest in the development of orally delivered non-peptide drugs. Here, we reveal unexpected overlap between signaling and regulation of the glucagon-like peptide-1 (GLP-1) receptor by the non-peptide agonist PF 06882961 and GLP-1 that was not observed for another compound, CHU-128. Compounds from these patent series, including PF 06882961, are currently in clinical trials for treatment of type 2 diabetes. High-resolution cryoelectron microscopy (cryo-EM) structures reveal that the binding sites for PF 06882961 and GLP-1 substantially overlap, whereas CHU-128 adopts a unique binding mode with a more open receptor conformation at the extracellular face. Structural differences involving extensive water-mediated hydrogen bond networks could be correlated to functional data to understand how PF 06882961, but not CHU-128, can closely mimic the pharmacological properties of GLP-1. These findings will facilitate rational structure-based discovery of non-peptide agonists targeting class B GPCRs. #1: Journal: Biorxiv / Year: 2020Title: Differential GLP-1R binding and activation by peptide and non-peptide agonists Authors: Zhang X / Belousoff MJ / Zhao P / Ang SY / Truong TT / Kooistra AJ / Underwood CR / Egebjerg T / Stewart GD / Liang YL / Glukhova A / Venugopal H / Christopoulos A / Furness SGB / Miller LJ ...Authors: Zhang X / Belousoff MJ / Zhao P / Ang SY / Truong TT / Kooistra AJ / Underwood CR / Egebjerg T / Stewart GD / Liang YL / Glukhova A / Venugopal H / Christopoulos A / Furness SGB / Miller LJ / Runge SR / Gloriam DE / Langmead CJ / Danev R / Sexton PM / Wootten D | ||||||||||||||||||
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Structure visualization
| Movie |
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| Structure viewer | EM map: SurfView Molmil Jmol/JSmol |
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Downloads & links
-EMDB archive
| Map data | emd_21992.map.gz | 272.4 MB | EMDB map data format | |
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| Header (meta data) | emd-21992-v30.xml emd-21992.xml | 37.3 KB 37.3 KB | Display Display | EMDB header |
| FSC (resolution estimation) | emd_21992_fsc.xml | 11.3 KB | Display | FSC data file |
| Images | emd_21992.png | 41.9 KB | ||
| Masks | emd_21992_msk_1.map | 125 MB | Mask map | |
| Filedesc metadata | emd-21992.cif.gz | 8.3 KB | ||
| Others | emd_21992_additional_1.map.gz emd_21992_additional_2.map.gz emd_21992_additional_3.map.gz emd_21992_half_map_1.map.gz emd_21992_half_map_2.map.gz | 31.5 MB 32.1 MB 98.3 MB 98.6 MB 98.6 MB | ||
| Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-21992 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-21992 | HTTPS FTP |
-Validation report
| Summary document | emd_21992_validation.pdf.gz | 938.8 KB | Display | EMDB validaton report |
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| Full document | emd_21992_full_validation.pdf.gz | 938.3 KB | Display | |
| Data in XML | emd_21992_validation.xml.gz | 19.1 KB | Display | |
| Data in CIF | emd_21992_validation.cif.gz | 24.6 KB | Display | |
| Arichive directory | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-21992 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-21992 | HTTPS FTP |
-Related structure data
| Related structure data | ![]() 6x18MC ![]() 6x19C ![]() 6x1aC C: citing same article ( M: atomic model generated by this map |
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| Similar structure data | |
| EM raw data | EMPIAR-10673 (Title: Cryo-EM of GLP-1 receptor bound to GLP-1 and Gs proteinData size: 1.9 TB Data #1: Non-gain-normalized LZW-TIFF compressed movies of GLP-1R-GLP-1 in a detergent micelle [micrographs - multiframe]) |
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Links
| EMDB pages | EMDB (EBI/PDBe) / EMDataResource |
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| Related items in Molecule of the Month |
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Map
| File | Download / File: emd_21992.map.gz / Format: CCP4 / Size: 290.8 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: 0.5 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_21992_msk_1.map | ||||||||||||
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-Additional map: #1
| File | emd_21992_additional_1.map | ||||||||||||
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-Additional map: Focussed refinement on extra-cellular domain
| File | emd_21992_additional_2.map | ||||||||||||
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| Annotation | Focussed refinement on extra-cellular domain | ||||||||||||
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-Additional map: unsharpened post-processed map
| File | emd_21992_additional_3.map | ||||||||||||
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| Annotation | unsharpened post-processed map | ||||||||||||
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-Half map: #2
| File | emd_21992_half_map_1.map | ||||||||||||
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-Half map: #1
| File | emd_21992_half_map_2.map | ||||||||||||
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Sample components
+Entire : GLP-1 peptide hormone bound to Glucagon-Like peptide-1 (GLP-1) Re...
+Supramolecule #1: GLP-1 peptide hormone bound to Glucagon-Like peptide-1 (GLP-1) Re...
+Supramolecule #2: Guanine nucleotide-binding protein G(s) subunit alpha isoforms sh...
+Supramolecule #3: Nanobody 35
+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: Nanobody35
+Macromolecule #5: Glucagon
+Macromolecule #6: Glucagon-like peptide 1 receptor
+Macromolecule #7: water
-Experimental details
-Structure determination
| Method | cryo EM |
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Processing | single particle reconstruction |
| Aggregation state | particle |
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Sample preparation
| Concentration | 3.5 mg/mL |
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| Buffer | pH: 7.4 |
| Vitrification | Cryogen name: ETHANE / Chamber humidity: 100 % / Chamber temperature: 277 K / Instrument: FEI VITROBOT MARK IV |
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Electron microscopy
| Microscope | FEI TITAN KRIOS |
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| Image recording | Film or detector model: GATAN K3 (6k x 4k) / Average electron dose: 60.0 e/Å2 |
| Electron beam | Acceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN |
| Electron optics | Illumination mode: SPOT SCAN / Imaging mode: BRIGHT FIELD |
| Experimental equipment | ![]() Model: Titan Krios / Image courtesy: FEI Company |
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About Yorodumi


Keywords
Homo sapiens (human)
Authors
Australia, 5 items
Citation

UCSF Chimera




































Z (Sec.)
Y (Row.)
X (Col.)





































































Trichoplusia ni (cabbage looper)

Processing

