| http://purl.uniprot.org/citations/18287102 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/18287102 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/18287102 | http://www.w3.org/2000/01/rdf-schema#comment | "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."xsd:string |
| http://purl.uniprot.org/citations/18287102 | http://purl.org/dc/terms/identifier | "doi:10.1074/jbc.m708740200"xsd:string |
| http://purl.uniprot.org/citations/18287102 | http://purl.org/dc/terms/identifier | "doi:10.1074/jbc.m708740200"xsd:string |
| http://purl.uniprot.org/citations/18287102 | http://purl.uniprot.org/core/author | "Lau J."xsd:string |
| http://purl.uniprot.org/citations/18287102 | http://purl.uniprot.org/core/author | "Lau J."xsd:string |
| http://purl.uniprot.org/citations/18287102 | http://purl.uniprot.org/core/author | "Runge S."xsd:string |
| http://purl.uniprot.org/citations/18287102 | http://purl.uniprot.org/core/author | "Runge S."xsd:string |
| http://purl.uniprot.org/citations/18287102 | http://purl.uniprot.org/core/author | "Rudolph R."xsd:string |
| http://purl.uniprot.org/citations/18287102 | http://purl.uniprot.org/core/author | "Rudolph R."xsd:string |
| http://purl.uniprot.org/citations/18287102 | http://purl.uniprot.org/core/author | "Madsen K."xsd:string |
| http://purl.uniprot.org/citations/18287102 | http://purl.uniprot.org/core/author | "Madsen K."xsd:string |
| http://purl.uniprot.org/citations/18287102 | http://purl.uniprot.org/core/author | "Thogersen H."xsd:string |
| http://purl.uniprot.org/citations/18287102 | http://purl.uniprot.org/core/author | "Thogersen H."xsd:string |
| http://purl.uniprot.org/citations/18287102 | http://purl.uniprot.org/core/date | "2008"xsd:gYear |
| http://purl.uniprot.org/citations/18287102 | http://purl.uniprot.org/core/date | "2008"xsd:gYear |
| http://purl.uniprot.org/citations/18287102 | http://purl.uniprot.org/core/name | "J. Biol. Chem."xsd:string |
| http://purl.uniprot.org/citations/18287102 | http://purl.uniprot.org/core/name | "J. Biol. Chem."xsd:string |
| http://purl.uniprot.org/citations/18287102 | http://purl.uniprot.org/core/pages | "11340-11347"xsd:string |
| http://purl.uniprot.org/citations/18287102 | http://purl.uniprot.org/core/pages | "11340-11347"xsd:string |
| http://purl.uniprot.org/citations/18287102 | http://purl.uniprot.org/core/title | "Crystal structure of the ligand-bound glucagon-like peptide-1 receptor extracellular domain."xsd:string |
| http://purl.uniprot.org/citations/18287102 | http://purl.uniprot.org/core/title | "Crystal structure of the ligand-bound glucagon-like peptide-1 receptor extracellular domain."xsd:string |
| http://purl.uniprot.org/citations/18287102 | http://purl.uniprot.org/core/volume | "283"xsd:string |
| http://purl.uniprot.org/citations/18287102 | http://purl.uniprot.org/core/volume | "283"xsd:string |