5e94
From Proteopedia
(Difference between revisions)
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| - | '''Unreleased structure''' | ||
| - | + | ==Antibody-bound Glucagon-like Peptide-1 receptor extracellular domain== | |
| + | <StructureSection load='5e94' size='340' side='right' caption='[[5e94]], [[Resolution|resolution]] 2.00Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[5e94]] is a 6 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5E94 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5E94 FirstGlance]. <br> | ||
| + | </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=5e94 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5e94 OCA], [http://pdbe.org/5e94 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5e94 RCSB], [http://www.ebi.ac.uk/pdbsum/5e94 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5e94 ProSAT]</span></td></tr> | ||
| + | </table> | ||
| + | == Function == | ||
| + | [[http://www.uniprot.org/uniprot/GLP1R_HUMAN GLP1R_HUMAN]] This is a receptor for glucagon-like peptide 1. The activity of this receptor is mediated by G proteins which activate adenylyl cyclase. | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | The Glucagon-like peptide-1 receptor (GLP-1R) is a member of the class B G protein-coupled receptor (GPCR) family and a well-established target for the treatment of type 2 diabetes. The N-terminal extracellular domain (ECD) of GLP-1R is important for GLP-1 binding and the crystal structure of the GLP-1/ECD complex was reported previously. The first structure of a class B GPCR transmembrane (TM) domain was solved recently, but the full length receptor structure is still not well understood. Here we describe the molecular details of antibody-mediated antagonism of the GLP-1R using both in vitro pharmacology and x-ray crystallography. We showed that the antibody Fab fragment (Fab 3F52) blocked the GLP-1 binding site of the ECD directly and thereby acts as a competitive antagonist of native GLP-1. Interestingly, Fab 3F52 also blocked a short peptide agonist believed to engage primarily the transmembrane and extracellular loop region of GLP-1R, whereas functionality of an allosteric small-molecule agonist was not inhibited. This study has implications for the structural understanding of the GLP-1R and related class B GPCRs, which is important for the development of new and improved therapeutics targeting these receptors. | ||
| - | + | Structural insight into antibody-mediated antagonism of the Glucagon-like peptide-1 Receptor.,Hennen S, Kodra JT, Soroka V, Krogh BO, Wu X, Kaastrup P, Orskov C, Ronn SG, Schluckebier G, Barbateskovic S, Gandhi PS, Reedtz-Runge S Sci Rep. 2016 May 19;6:26236. doi: 10.1038/srep26236. PMID:27196125<ref>PMID:27196125</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | + | </div> | |
| - | + | <div class="pdbe-citations 5e94" style="background-color:#fffaf0;"></div> | |
| + | == References == | ||
| + | <references/> | ||
| + | __TOC__ | ||
| + | </StructureSection> | ||
[[Category: Reedtz-Runge, S]] | [[Category: Reedtz-Runge, S]] | ||
| + | [[Category: Schluckebier, G]] | ||
[[Category: Soroka, V]] | [[Category: Soroka, V]] | ||
| + | [[Category: Antibody antagonist glp-1 receptor]] | ||
| + | [[Category: Immune system]] | ||
| + | [[Category: Membrane protein]] | ||
Revision as of 06:50, 10 September 2016
Antibody-bound Glucagon-like Peptide-1 receptor extracellular domain
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