3c59
From Proteopedia
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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== | ||
| + | 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. | ||
==About this Structure== | ==About this Structure== | ||
3C59 is a [[Protein complex]] structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3C59 OCA]. | 3C59 is a [[Protein complex]] structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3C59 OCA]. | ||
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| + | ==Reference== | ||
| + | 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:[http://www.ncbi.nlm.nih.gov/pubmed/18287102 18287102] | ||
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Protein complex]] | [[Category: Protein complex]] | ||
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[[Category: Transducer]] | [[Category: Transducer]] | ||
[[Category: Transmembrane]] | [[Category: Transmembrane]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed May 7 08:59:15 2008'' |
Revision as of 05:59, 7 May 2008
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| 3c59, resolution 2.30Å () | |||||||||
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| Gene: | Glucagon-like peptide-1 receptor(GLP1R) (Homo sapiens) | ||||||||
| Related: | 3c5t | ||||||||
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| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||||
Crystal structure of the ligand-bound glucagon-like peptide-1 receptor extracellular domain
Overview
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.
About this Structure
3C59 is a Protein complex structure of sequences from Homo sapiens. Full crystallographic information is available from OCA.
Reference
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 Page seeded by OCA on Wed May 7 08:59:15 2008
Categories: Homo sapiens | Protein complex | Runge, S. | Amidation | Cleavage on pair of basic residue | G-protein coupled receptor | Glycoprotein | Ligand-bound g protein-coupled receptor | Membrane | Pharmaceutical | Polymorphism | Secreted | Signaling protein/signaling protein complex | Transducer | Transmembrane
