2qkh: Difference between revisions

Revision as of 15:07, 4 May 2008

Crystal structure of the extracellular domain of human GIP receptor in complex with the hormone GIP

OverviewOverview

Incretins, endogenous polypeptide hormones released in response to food intake, potentiate insulin secretion from pancreatic beta cells after oral glucose ingestion (the incretin effect). This response is signaled by the two peptide hormones glucose-dependent insulinotropic polypeptide (GIP) (also known as gastric inhibitory polypeptide) and glucagon-like peptide 1 through binding and activation of their cognate class 2 G protein-coupled receptors (GPCRs). Because the incretin effect is lost or significantly reduced in patients with type 2 diabetes mellitus, glucagon-like peptide 1 and GIP have attracted considerable attention for their potential in antidiabetic therapy. A paucity of structural information precludes a detailed understanding of the processes of hormone binding and receptor activation, hampering efforts to develop novel pharmaceuticals. Here we report the crystal structure of the complex of human GIP receptor extracellular domain (ECD) with its agonist, the incretin GIP(1-42). The hormone binds in an alpha-helical conformation in a surface groove of the ECD largely through hydrophobic interactions. The N-terminal ligand residues would remain free to interact with other parts of the receptor. Thermodynamic data suggest that binding is concomitant with structural organization of the hormone, resulting in a complex mode of receptor-ligand recognition. The presentation of a well structured, alpha-helical ligand by the ECD is expected to be conserved among other hormone receptors of this class.

About this StructureAbout this Structure

2QKH is a Protein complex structure of sequences from Homo sapiens. Full crystallographic information is available from OCA.

ReferenceReference

Crystal structure of the incretin-bound extracellular domain of a G protein-coupled receptor., Parthier C, Kleinschmidt M, Neumann P, Rudolph R, Manhart S, Schlenzig D, Fanghanel J, Rahfeld JU, Demuth HU, Stubbs MT, Proc Natl Acad Sci U S A. 2007 Aug 28;104(35):13942-7. Epub 2007 Aug 21. PMID:17715056 Page seeded by OCA on Sun May 4 15:07:00 2008

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OCA

@@ Line 1: / Line 1: @@
 [[Image:2qkh.jpg|left|200px]]
- {{Structure
+<!--
-|PDB= 2qkh |SIZE=350|CAPTION= <scene name='initialview01'>2qkh</scene>, resolution 1.900&Aring;
+The line below this paragraph, containing "STRUCTURE_2qkh", creates the "Structure Box" on the page.
-|SITE=
+You may change the PDB parameter (which sets the PDB file loaded into the applet)
-|LIGAND= <scene name='pdbligand=QKH:METHYL-CYCLO-HEPTA-AMYLOSE'>QKH</scene>, <scene name='pdbligand=TAR:D(-)-TARTARIC+ACID'>TAR</scene>
+or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
-|ACTIVITY=
+or leave the SCENE parameter empty for the default display.
-|GENE= GIPR ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])
+-->
-|DOMAIN=
+{{STRUCTURE_2qkh|  PDB=2qkh  |  SCENE=  }}
-|RELATEDENTRY=
-|RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2qkh FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2qkh OCA], [http://www.ebi.ac.uk/pdbsum/2qkh PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=2qkh RCSB]</span>
-}}
 '''Crystal structure of the extracellular domain of human GIP receptor in complex with the hormone GIP'''
@@ Line 35: / Line 32: @@
 [[Category: Schlenzig, D.]]
 [[Category: Stubbs, M T.]]
-[[Category: alternative splicing]]
+[[Category: Alternative splicing]]
-[[Category: cleavage on pair of basic residue]]
+[[Category: Cleavage on pair of basic residue]]
-[[Category: diabetes]]
+[[Category: Diabetes]]
-[[Category: ecd]]
+[[Category: Ecd]]
-[[Category: extracellular domain]]
+[[Category: Extracellular domain]]
-[[Category: g-protein coupled receptor]]
+[[Category: G-protein coupled receptor]]
-[[Category: glugacon receptor family]]
+[[Category: Glugacon receptor family]]
-[[Category: glycoprotein]]
+[[Category: Glycoprotein]]
-[[Category: gpcr]]
+[[Category: Gpcr]]
-[[Category: helix formation]]
+[[Category: Helix formation]]
-[[Category: hormone recognition fold]]
+[[Category: Hormone recognition fold]]
-[[Category: hormone-gpcr complex]]
+[[Category: Hormone-gpcr complex]]
-[[Category: incretin]]
+[[Category: Incretin]]
-[[Category: ligand binding domain]]
+[[Category: Ligand binding domain]]
-[[Category: membrane]]
+[[Category: Membrane]]
-[[Category: polymorphism]]
+[[Category: Polymorphism]]
-[[Category: signaling protein/hormone complex]]
+[[Category: Signaling protein/hormone complex]]
-[[Category: transducer]]
+[[Category: Transducer]]
-[[Category: transmembrane]]
+[[Category: Transmembrane]]
+''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun May  4 15:07:00 2008''
-''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Mar 31 04:50:17 2008''