5otx: Difference between revisions
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==Extracellular domain of GLP-1 receptor in complex with GLP-1 variant Ala8Cys/Thr11Cys== | ==Extracellular domain of GLP-1 receptor in complex with GLP-1 variant Ala8Cys/Thr11Cys== | ||
<StructureSection load='5otx' size='340' side='right' caption='[[5otx]], [[Resolution|resolution]] 2.00Å' scene=''> | <StructureSection load='5otx' size='340' side='right'caption='[[5otx]], [[Resolution|resolution]] 2.00Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[5otx]] is a 4 chain structure with sequence from [ | <table><tr><td colspan='2'>[[5otx]] is a 4 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=5OTX OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5OTX FirstGlance]. <br> | ||
</td></tr><tr id=' | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2Å</td></tr> | ||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[ | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=5otx FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5otx OCA], [https://pdbe.org/5otx PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5otx RCSB], [https://www.ebi.ac.uk/pdbsum/5otx PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5otx ProSAT]</span></td></tr> | ||
</table> | </table> | ||
== Function == | == Function == | ||
[ | [https://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;"> | <div style="background-color:#fffaf0;"> | ||
== Publication Abstract from PubMed == | == Publication Abstract from PubMed == | ||
| Line 18: | Line 18: | ||
</div> | </div> | ||
<div class="pdbe-citations 5otx" style="background-color:#fffaf0;"></div> | <div class="pdbe-citations 5otx" style="background-color:#fffaf0;"></div> | ||
==See Also== | |||
*[[Glucagon|Glucagon]] | |||
*[[Glucagon-like peptide receptor 3D structures|Glucagon-like peptide receptor 3D structures]] | |||
== References == | == References == | ||
<references/> | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: | [[Category: Homo sapiens]] | ||
[[Category: | [[Category: Large Structures]] | ||
[[Category: | [[Category: Mortensen S]] | ||
Latest revision as of 04:24, 28 December 2023
Extracellular domain of GLP-1 receptor in complex with GLP-1 variant Ala8Cys/Thr11CysExtracellular domain of GLP-1 receptor in complex with GLP-1 variant Ala8Cys/Thr11Cys
Structural highlights
FunctionGLP1R_HUMAN This is a receptor for glucagon-like peptide 1. The activity of this receptor is mediated by G proteins which activate adenylyl cyclase. Publication Abstract from PubMedPeptide agonists acting on the glucagon-like peptide 1 receptor (GLP-1R) promote glucose-dependent insulin release and therefore represent important therapeutic agents for type 2 diabetes (T2D). Previous data indicated that an N-terminal type II beta-turn motif might be an important feature for agonists acting on the GLP-1R. In contrast, recent publications reporting the structure of the full-length GLP-1R have shown the N-terminus of receptor-bound agonists in an alpha-helical conformation. To reconcile these conflicting results, we prepared N-terminally constrained analogues of glucagon-like peptide 1 (GLP-1) and exendin-4 and evaluated their receptor affinity and functionality in vitro; we then examined their crystal structures in complex with the extracellular domain of the GLP-1R and used molecular modeling and molecular dynamics simulations for further investigations. We report that the peptides' N-termini in all determined crystal structures adopted a type II beta-turn conformation, but in vitro potency varied several thousand-fold across the series. Potency correlated better with alpha-helicity in our computational model, although we have found that the energy barrier between the two mentioned conformations is low in our most potent analogues and the flexibility of the N-terminus is highlighted by the dynamics simulations. alpha-Helix or beta-Turn? An Investigation into N-Terminally Constrained Analogues of Glucagon-like Peptide 1 (GLP-1) and Exendin-4.,Oddo A, Mortensen S, Thogersen H, De Maria L, Hennen S, McGuire JN, Kofoed J, Linderoth L, Reedtz-Runge S Biochemistry. 2018 Jun 21. doi: 10.1021/acs.biochem.8b00105. PMID:29877701[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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