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| | ==Crystal structure of the ligand-bound glucagon-like peptide-1 receptor extracellular domain== | | ==Crystal structure of the ligand-bound glucagon-like peptide-1 receptor extracellular domain== |
| - | <StructureSection load='3c5t' size='340' side='right' caption='[[3c5t]], [[Resolution|resolution]] 2.10Å' scene=''> | + | <StructureSection load='3c5t' size='340' side='right'caption='[[3c5t]], [[Resolution|resolution]] 2.10Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[3c5t]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3C5T OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3C5T FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[3c5t]] 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=3C5T OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3C5T FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=10M:DECYL+4-O-ALPHA-D-GLUCOPYRANOSYL-1-THIO-BETA-D-GLUCOPYRANOSIDE'>10M</scene></td></tr> | + | </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='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3c59|3c59]]</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]]</div></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">Glucagon-like peptide-1 receptor(GLP1R) ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr> | + | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">Glucagon-like peptide-1 receptor(GLP1R) ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr> |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3c5t FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3c5t OCA], [http://pdbe.org/3c5t PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3c5t RCSB], [http://www.ebi.ac.uk/pdbsum/3c5t PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3c5t 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=3c5t FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3c5t OCA], [https://pdbe.org/3c5t PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3c5t RCSB], [https://www.ebi.ac.uk/pdbsum/3c5t PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3c5t ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://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. [[http://www.uniprot.org/uniprot/EXE4_HELSU EXE4_HELSU]] Venom protein that mimics the incretin hormone glucagon-like peptide 1 (GLP-1). It stimulates insulin synthesis and secretion, protects against beta-cell apoptosis in response to different insults, and promotes beta-cell proliferation. It also promotes satiety, reduces food intake, reduces fat deposition, reduces body weight and inhibits gastric emptying. Interacts with GLP-1 receptor (GLP1R). Induces hypotension that is mediated by relaxation of cardiac smooth muscle.<ref>PMID:8405712</ref> <ref>PMID:19837656</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. [[https://www.uniprot.org/uniprot/EXE4_HELSU EXE4_HELSU]] Venom protein that mimics the incretin hormone glucagon-like peptide 1 (GLP-1). It stimulates insulin synthesis and secretion, protects against beta-cell apoptosis in response to different insults, and promotes beta-cell proliferation. It also promotes satiety, reduces food intake, reduces fat deposition, reduces body weight and inhibits gastric emptying. Interacts with GLP-1 receptor (GLP1R). Induces hypotension that is mediated by relaxation of cardiac smooth muscle.<ref>PMID:8405712</ref> <ref>PMID:19837656</ref> |
| | == Evolutionary Conservation == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
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| | </div> | | </div> |
| | <div class="pdbe-citations 3c5t" style="background-color:#fffaf0;"></div> | | <div class="pdbe-citations 3c5t" style="background-color:#fffaf0;"></div> |
| | + | |
| | + | ==See Also== |
| | + | *[[Glucagon-like peptide 1 receptor|Glucagon-like peptide 1 receptor]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
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| | </StructureSection> | | </StructureSection> |
| | [[Category: Human]] | | [[Category: Human]] |
| | + | [[Category: Large Structures]] |
| | [[Category: Runge, S]] | | [[Category: Runge, S]] |
| | [[Category: Amidation]] | | [[Category: Amidation]] |
| 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. [EXE4_HELSU] Venom protein that mimics the incretin hormone glucagon-like peptide 1 (GLP-1). It stimulates insulin synthesis and secretion, protects against beta-cell apoptosis in response to different insults, and promotes beta-cell proliferation. It also promotes satiety, reduces food intake, reduces fat deposition, reduces body weight and inhibits gastric emptying. Interacts with GLP-1 receptor (GLP1R). Induces hypotension that is mediated by relaxation of cardiac smooth muscle.[1] [2]
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
The glucagon-like peptide-1 receptor (GLP-1R) belongs to Family B1 of the seven-transmembrane G protein-coupled receptors, and its natural agonist ligand is the peptide hormone glucagon-like peptide-1 (GLP-1). GLP-1 is involved in glucose homeostasis, and activation of GLP-1R in the plasma membrane of pancreatic beta-cells potentiates glucose-dependent insulin secretion. The N-terminal extracellular domain (nGLP-1R) is an important ligand binding domain that binds GLP-1 and the homologous peptide Exendin-4 with differential affinity. Exendin-4 has a C-terminal extension of nine amino acid residues known as the "Trp cage", which is absent in GLP-1. The Trp cage was believed to interact with nGLP-1R and thereby explain the superior affinity of Exendin-4. However, the molecular details that govern ligand binding and specificity of nGLP-1R remain undefined. Here we report the crystal structure of human nGLP-1R in complex with the antagonist Exendin-4(9-39) solved by the multiwavelength anomalous dispersion method to 2.2A resolution. The structure reveals that Exendin-4(9-39) is an amphipathic alpha-helix forming both hydrophobic and hydrophilic interactions with nGLP-1R. The Trp cage of Exendin-4 is not involved in binding to nGLP-1R. The hydrophobic binding site of nGLP-1R is defined by discontinuous segments including primarily a well defined alpha-helix in the N terminus of nGLP-1R and a loop between two antiparallel beta-strands. The structure provides for the first time detailed molecular insight into ligand binding of the human GLP-1 receptor, an established target for treatment of type 2 diabetes.
Crystal structure of the ligand-bound glucagon-like peptide-1 receptor extracellular domain.,Runge S, Thogersen H, Madsen K, Lau J, Rudolph R J Biol Chem. 2008 Apr 25;283(17):11340-7. Epub 2008 Feb 20. PMID:18287102[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Thorens B, Porret A, Buhler L, Deng SP, Morel P, Widmann C. Cloning and functional expression of the human islet GLP-1 receptor. Demonstration that exendin-4 is an agonist and exendin-(9-39) an antagonist of the receptor. Diabetes. 1993 Nov;42(11):1678-82. PMID:8405712
- ↑ Fry BG, Roelants K, Winter K, Hodgson WC, Griesman L, Kwok HF, Scanlon D, Karas J, Shaw C, Wong L, Norman JA. Novel venom proteins produced by differential domain-expression strategies in beaded lizards and gila monsters (genus Heloderma). Mol Biol Evol. 2010 Feb;27(2):395-407. doi: 10.1093/molbev/msp251. Epub 2009 Oct , 15. PMID:19837656 doi:http://dx.doi.org/10.1093/molbev/msp251
- ↑ Runge S, Thogersen H, Madsen K, Lau J, Rudolph R. Crystal structure of the ligand-bound glucagon-like peptide-1 receptor extracellular domain. J Biol Chem. 2008 Apr 25;283(17):11340-7. Epub 2008 Feb 20. PMID:18287102 doi:10.1074/jbc.M708740200
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