| http://purl.uniprot.org/citations/17444618 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/17444618 | http://www.w3.org/2000/01/rdf-schema#comment | "Glucagon-like peptide-1 (GLP-1) and exendin-4 (Ex4) are homologous peptides with established potential for treatment of type 2 diabetes. They bind and activate the pancreatic GLP-1 receptor (GLP-1R) with similar affinity and potency and thereby promote insulin secretion in a glucose-dependent manner. GLP-1R belongs to family B of the seven transmembrane G-protein coupled receptors. The N-terminal extracellular domain (nGLP-1R) is a ligand binding domain with differential affinity for Ex4 and GLP-1: low affinity for GLP-1 and high affinity for exendin-4. The superior affinity of nGLP-1R for Ex4 was previously explained by an additional interaction between nGLP-1R and the C-terminal Trp-cage of Ex4. In this study we have combined biophysical and pharmacological approaches thus relating structural properties of the ligands in solution to their relative binding affinity for nGLP-1R. We used both a tracer competition assay and ligand-induced thermal stabilization of nGLP-1R to measure the relative affinity of full length, truncated, and chimeric ligands for soluble refolded nGLP-1R. The ligands in solution and the conformational consequences of ligand binding to nGLP-1R were characterized by circular dichroism and fluorescence spectroscopy. We found a correlation between the helical content of the free ligands and their relative binding affinity for nGLP-1R, supporting the hypothesis that the ligands are helical at least in the segment that binds to nGLP-1R. The Trp-cage of Ex4 was not necessary to maintain a superior helicity of Ex4 compared to GLP-1. The results suggest that the differential affinity of nGLP-1R is explained almost entirely by divergent residues in the central part of the ligands: Leu10-Gly30 of Ex4 and Val16-Arg36 of GLP-1. In view of our results it appears that the Trp-cage plays only a minor role for the interaction between Ex4 and nGLP-1R and for the differential affinity of nGLP-1R for GLP-1 and Ex4."xsd:string |
| http://purl.uniprot.org/citations/17444618 | http://purl.org/dc/terms/identifier | "doi:10.1021/bi062309m"xsd:string |
| http://purl.uniprot.org/citations/17444618 | http://purl.uniprot.org/core/author | "Lau J."xsd:string |
| http://purl.uniprot.org/citations/17444618 | http://purl.uniprot.org/core/author | "Runge S."xsd:string |
| http://purl.uniprot.org/citations/17444618 | http://purl.uniprot.org/core/author | "Rudolph R."xsd:string |
| http://purl.uniprot.org/citations/17444618 | http://purl.uniprot.org/core/author | "Knudsen S.M."xsd:string |
| http://purl.uniprot.org/citations/17444618 | http://purl.uniprot.org/core/author | "Madsen K."xsd:string |
| http://purl.uniprot.org/citations/17444618 | http://purl.uniprot.org/core/author | "Thogersen H."xsd:string |
| http://purl.uniprot.org/citations/17444618 | http://purl.uniprot.org/core/author | "Jeppesen C.B."xsd:string |
| http://purl.uniprot.org/citations/17444618 | http://purl.uniprot.org/core/author | "Schimmer S."xsd:string |
| http://purl.uniprot.org/citations/17444618 | http://purl.uniprot.org/core/author | "Oschmann J."xsd:string |
| http://purl.uniprot.org/citations/17444618 | http://purl.uniprot.org/core/author | "Schiodt C.B."xsd:string |
| http://purl.uniprot.org/citations/17444618 | http://purl.uniprot.org/core/date | "2007"xsd:gYear |
| http://purl.uniprot.org/citations/17444618 | http://purl.uniprot.org/core/name | "Biochemistry"xsd:string |
| http://purl.uniprot.org/citations/17444618 | http://purl.uniprot.org/core/pages | "5830-5840"xsd:string |
| http://purl.uniprot.org/citations/17444618 | http://purl.uniprot.org/core/title | "Differential structural properties of GLP-1 and exendin-4 determine their relative affinity for the GLP-1 receptor N-terminal extracellular domain."xsd:string |
| http://purl.uniprot.org/citations/17444618 | http://purl.uniprot.org/core/volume | "46"xsd:string |
| http://purl.uniprot.org/citations/17444618 | http://www.w3.org/2004/02/skos/core#exactMatch | http://purl.uniprot.org/pubmed/17444618 |
| http://purl.uniprot.org/citations/17444618 | http://xmlns.com/foaf/0.1/primaryTopicOf | https://pubmed.ncbi.nlm.nih.gov/17444618 |
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| http://purl.uniprot.org/uniprot/#_A0A142FHB8-mappedCitation-17444618 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/17444618 |
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| http://purl.uniprot.org/uniprot/#_P43220-mappedCitation-17444618 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/17444618 |