4hj0: Difference between revisions
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4hj0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4hj0 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4hj0 RCSB], [http://www.ebi.ac.uk/pdbsum/4hj0 PDBsum]</span></td></tr> | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4hj0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4hj0 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4hj0 RCSB], [http://www.ebi.ac.uk/pdbsum/4hj0 PDBsum]</span></td></tr> | ||
</table> | </table> | ||
== Function == | |||
[[http://www.uniprot.org/uniprot/GIPR_HUMAN GIPR_HUMAN]] This is a receptor for GIP. The activity of this receptor is mediated by G proteins which activate adenylyl cyclase. | |||
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== Publication Abstract from PubMed == | == Publication Abstract from PubMed == | ||
Revision as of 08:23, 25 December 2014
Crystal structure of the human GIPr ECD in complex with Gipg013 Fab at 3-A resolutionCrystal structure of the human GIPr ECD in complex with Gipg013 Fab at 3-A resolution
Structural highlights
Function[GIPR_HUMAN] This is a receptor for GIP. The activity of this receptor is mediated by G proteins which activate adenylyl cyclase. Publication Abstract from PubMedGlucose-dependent insulinotropic polypeptide (GIP) is an endogenous hormonal factor (incretin) that upon binding to its receptor (GIPr; a class B GPCR), stimulates insulin secretion by beta cells in the pancreas, There has been a lack of potent inhibitors of the GIPr with prolonged in vivo exposure, to investigate GIP biology. Here we describe here the generation of an antagonizing antibody to the GIPr, using phage and ribosome display libraries. Gipg013 is a specific competitive antagonist with equally high potencies to mouse, rat, dog and human GIP receptors with a Ki of 7 nM for the human GIPr. Gipg013 antagonises the GIP receptor and inhibits GIP induced insulin secretion in vivo. A crystal structure of Gipg013 Fab in complex with the human GIPr ECD indicates that the antibody binds through a series of hydrogen bonds from the CDRs of Gipg013 Fab to the N-terminal alpha-helix of GIPr extracellular domain (ECD) as well as to residues around its highly conserved glucagon receptor sub-family recognition fold. The antibody epitope overlaps with the GIP binding site on GIPr ECD ensuring competitive antagonism of the receptor. This well characterized antagonizing antibody to the GIPr will be useful as a tool to further understand the biological roles of GIP. Structural and Pharmacological Characterisation of Novel Potent and Selective Monoclonal Antibody Antagonists of Glucose-Dependent Insulinotropic Polypeptide Receptor.,Ravn P, Madhurantakam C, Kunze S, Matthews E, Priest C, O'brien S, Collinson A, Papworth M, Fritsch-Fredin M, Jermutus L, Benthem L, Gruetter M, Jackson RH J Biol Chem. 2013 May 20. PMID:23689510[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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