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| | ==Crystal structure of the human GIPr ECD in complex with Gipg013 Fab at 3-A resolution== | | ==Crystal structure of the human GIPr ECD in complex with Gipg013 Fab at 3-A resolution== |
| - | <StructureSection load='4hj0' size='340' side='right' caption='[[4hj0]], [[Resolution|resolution]] 3.00Å' scene=''> | + | <StructureSection load='4hj0' size='340' side='right'caption='[[4hj0]], [[Resolution|resolution]] 3.00Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4hj0]] is a 6 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4HJ0 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4HJ0 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4hj0]] is a 6 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4HJ0 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4HJ0 FirstGlance]. <br> |
| - | </td></tr><tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">GIPR ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr> | + | </td></tr><tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=4hj0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4hj0 OCA], [https://pdbe.org/4hj0 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4hj0 RCSB], [https://www.ebi.ac.uk/pdbsum/4hj0 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4hj0 ProSAT]</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://pdbe.org/4hj0 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4hj0 RCSB], [http://www.ebi.ac.uk/pdbsum/4hj0 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4hj0 ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == 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. | + | [https://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. |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | ==See Also== | | ==See Also== |
| - | *[[3D structures of monoclonal antibody|3D structures of monoclonal antibody]] | + | *[[Antibody 3D structures|Antibody 3D structures]] |
| | + | *[[Glucose-dependent Insulinotropic Polypeptide Receptor|Glucose-dependent Insulinotropic Polypeptide Receptor]] |
| | + | *[[Monoclonal Antibodies 3D structures|Monoclonal Antibodies 3D structures]] |
| | + | *[[3D structures of human antibody|3D structures of human antibody]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| - | [[Category: Gruetter, M G]] | + | [[Category: Large Structures]] |
| - | [[Category: Jackson, R H]] | + | [[Category: Gruetter MG]] |
| - | [[Category: Madhurantakam, C]] | + | [[Category: Jackson RH]] |
| - | [[Category: Ravn, P]] | + | [[Category: Madhurantakam C]] |
| - | [[Category: Glucagon receptor sub-family recognition fold]] | + | [[Category: Ravn P]] |
| - | [[Category: Immune system]]
| + | |
| 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 PubMed
Glucose-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 Also
References
- ↑ 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. Structural and Pharmacological Characterisation of Novel Potent and Selective Monoclonal Antibody Antagonists of Glucose-Dependent Insulinotropic Polypeptide Receptor. J Biol Chem. 2013 May 20. PMID:23689510 doi:10.1074/jbc.M112.426288
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