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| {{STRUCTURE_3c59| PDB=3c59 | SCENE= }} | | {{STRUCTURE_3c59| PDB=3c59 | SCENE= }} |
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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=== |
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| ==Overview==
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| 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. | | The line below this paragraph, {{ABSTRACT_PUBMED_18287102}}, adds the Publication Abstract to the page |
| | (as it appears on PubMed at http://www.pubmed.gov), where 18287102 is the PubMed ID number. |
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| | {{ABSTRACT_PUBMED_18287102}} |
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| ==About this Structure== | | ==About this Structure== |
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| [[Category: Transducer]] | | [[Category: Transducer]] |
| [[Category: Transmembrane]] | | [[Category: Transmembrane]] |
| ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed May 7 08:59:15 2008'' | | |
| | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Jul 27 18:16:30 2008'' |