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| | <StructureSection load='3iol' size='340' side='right'caption='[[3iol]], [[Resolution|resolution]] 2.10Å' scene=''> | | <StructureSection load='3iol' size='340' side='right'caption='[[3iol]], [[Resolution|resolution]] 2.10Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[3iol]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3IOL OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3IOL FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[3iol]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3IOL OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3IOL FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=10M:DECYL+4-O-ALPHA-D-GLUCOPYRANOSYL-1-THIO-BETA-D-GLUCOPYRANOSIDE'>10M</scene></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.1Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[3c59|3c59]], [[3c5t|3c5t]]</div></td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=10M:DECYL+4-O-ALPHA-D-GLUCOPYRANOSYL-1-THIO-BETA-D-GLUCOPYRANOSIDE'>10M</scene></td></tr> |
| | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=3iol FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3iol OCA], [https://pdbe.org/3iol PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3iol RCSB], [https://www.ebi.ac.uk/pdbsum/3iol PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3iol ProSAT]</span></td></tr> | | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=3iol FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3iol OCA], [https://pdbe.org/3iol PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3iol RCSB], [https://www.ebi.ac.uk/pdbsum/3iol PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3iol ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[https://www.uniprot.org/uniprot/GLP1R_HUMAN GLP1R_HUMAN]] This is a receptor for glucagon-like peptide 1. The activity of this receptor is mediated by G proteins which activate adenylyl cyclase. [[https://www.uniprot.org/uniprot/GLUC_HUMAN GLUC_HUMAN]] Glucagon plays a key role in glucose metabolism and homeostasis. Regulates blood glucose by increasing gluconeogenesis and decreasing glycolysis. A counterregulatory hormone of insulin, raises plasma glucose levels in response to insulin-induced hypoglycemia. Plays an important role in initiating and maintaining hyperglycemic conditions in diabetes.<ref>PMID:8482423</ref> <ref>PMID:14557443</ref> <ref>PMID:14632334</ref> GLP-1 is a potent stimulator of glucose-dependent insulin release. Play important roles on gastric motility and the suppression of plasma glucagon levels. May be involved in the suppression of satiety and stimulation of glucose disposal in peripheral tissues, independent of the actions of insulin. Have growth-promoting activities on intestinal epithelium. May also regulate the hypothalamic pituitary axis (HPA) via effects on LH, TSH, CRH, oxytocin, and vasopressin secretion. Increases islet mass through stimulation of islet neogenesis and pancreatic beta cell proliferation. Inhibits beta cell apoptosis.<ref>PMID:8482423</ref> <ref>PMID:14557443</ref> <ref>PMID:14632334</ref> GLP-2 stimulates intestinal growth and up-regulates villus height in the small intestine, concomitant with increased crypt cell proliferation and decreased enterocyte apoptosis. The gastrointestinal tract, from the stomach to the colon is the principal target for GLP-2 action. Plays a key role in nutrient homeostasis, enhancing nutrient assimilation through enhanced gastrointestinal function, as well as increasing nutrient disposal. Stimulates intestinal glucose transport and decreases mucosal permeability.<ref>PMID:8482423</ref> <ref>PMID:14557443</ref> <ref>PMID:14632334</ref> Oxyntomodulin significantly reduces food intake. Inhibits gastric emptying in humans. Suppression of gastric emptying may lead to increased gastric distension, which may contribute to satiety by causing a sensation of fullness.<ref>PMID:8482423</ref> <ref>PMID:14557443</ref> <ref>PMID:14632334</ref> Glicentin may modulate gastric acid secretion and the gastro-pyloro-duodenal activity. May play an important role in intestinal mucosal growth in the early period of life.<ref>PMID:8482423</ref> <ref>PMID:14557443</ref> <ref>PMID:14632334</ref>
| + | [https://www.uniprot.org/uniprot/GLP1R_HUMAN GLP1R_HUMAN] This is a receptor for glucagon-like peptide 1. The activity of this receptor is mediated by G proteins which activate adenylyl cyclase. |
| | == Evolutionary Conservation == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
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| | ==See Also== | | ==See Also== |
| | *[[Glucagon-like peptide 1 receptor|Glucagon-like peptide 1 receptor]] | | *[[Glucagon-like peptide 1 receptor|Glucagon-like peptide 1 receptor]] |
| | + | *[[Glucagon-like peptide receptor 3D structures|Glucagon-like peptide receptor 3D structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Reedtz-Runge, S]] | + | [[Category: Reedtz-Runge S]] |
| - | [[Category: Amidation]]
| + | |
| - | [[Category: Cell membrane]]
| + | |
| - | [[Category: Cleavage on pair of basic residue]]
| + | |
| - | [[Category: Disulfide bond]]
| + | |
| - | [[Category: G-protein coupled receptor]]
| + | |
| - | [[Category: Glycoprotein]]
| + | |
| - | [[Category: Hormone]]
| + | |
| - | [[Category: Membrane]]
| + | |
| - | [[Category: Receptor]]
| + | |
| - | [[Category: Receptor-ligand complex]]
| + | |
| - | [[Category: Secreted]]
| + | |
| - | [[Category: Signaling protein-signaling protein complex]]
| + | |
| - | [[Category: Transducer]]
| + | |
| - | [[Category: Transmembrane]]
| + | |
| Structural highlights
Function
GLP1R_HUMAN This is a receptor for glucagon-like peptide 1. The activity of this receptor is mediated by G proteins which activate adenylyl cyclase.
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
GLP-1 (glucagon-like peptide-1) is an incretin released from intestinal L-cells in response to food intake. Activation of the GLP-1 receptor potentiates the synthesis and release of insulin from pancreatic beta-cells in a glucose-dependent manner. The GLP-1 receptor belongs to class B of the G-protein-coupled receptors, a subfamily characterized by a large N-terminal extracellular ligand binding domain. Exendin-4 and GLP-1 are 50% identical, and exendin-4 is a full agonist with similar affinity and potency for the GLP-1 receptor. We recently solved the crystal structure of the GLP-1 receptor extracellular domain in complex with the competitive antagonist exendin-4(9-39). Interestingly, the isolated extracellular domain binds exendin-4 with much higher affinity than the endogenous agonist GLP-1. Here, we have solved the crystal structure of the extracellular domain in complex with GLP-1 to 2.1 Aresolution. The structure shows that important hydrophobic ligand-receptor interactions are conserved in agonist- and antagonist-bound forms of the extracellular domain, but certain residues in the ligand-binding site adopt a GLP-1-specific conformation. GLP-1 is a kinked but continuous alpha-helix from Thr(13) to Val(33) when bound to the extracellular domain. We supplemented the crystal structure with site-directed mutagenesis to link the structural information of the isolated extracellular domain with the binding properties of the full-length receptor. The data support the existence of differences in the binding modes of GLP-1 and exendin-4 on the full-length GLP-1 receptor.
Crystal structure of glucagon-like peptide-1 in complex with the extracellular domain of the glucagon-like peptide-1 receptor.,Underwood CR, Garibay P, Knudsen LB, Hastrup S, Peters GH, Rudolph R, Reedtz-Runge S J Biol Chem. 2010 Jan 1;285(1):723-30. Epub 2009 Oct 27. PMID:19861722[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Underwood CR, Garibay P, Knudsen LB, Hastrup S, Peters GH, Rudolph R, Reedtz-Runge S. Crystal structure of glucagon-like peptide-1 in complex with the extracellular domain of the glucagon-like peptide-1 receptor. J Biol Chem. 2010 Jan 1;285(1):723-30. Epub 2009 Oct 27. PMID:19861722 doi:10.1074/jbc.M109.033829
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