7s1m: Difference between revisions
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==Ex4-D-Ala bound to the glucagon-like peptide-1 receptor/g protein complex (conformer 1)== | |||
<StructureSection load='7s1m' size='340' side='right'caption='[[7s1m]], [[Resolution|resolution]] 2.41Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[7s1m]] is a 6 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens], [https://en.wikipedia.org/wiki/Lama_glama Lama glama] and [https://en.wikipedia.org/wiki/Synthetic_construct Synthetic construct]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7S1M OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7S1M FirstGlance]. <br> | |||
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 2.41Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=DAL:D-ALANINE'>DAL</scene></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=7s1m FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7s1m OCA], [https://pdbe.org/7s1m PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7s1m RCSB], [https://www.ebi.ac.uk/pdbsum/7s1m PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7s1m ProSAT]</span></td></tr> | |||
</table> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Recent advances in G-protein-coupled receptor (GPCR) structural elucidation have strengthened previous hypotheses that multidimensional signal propagation mediated by these receptors depends, in part, on their conformational mobility; however, the relationship between receptor function and static structures is inherently uncertain. Here, we examine the contribution of peptide agonist conformational plasticity to activation of the glucagon-like peptide 1 receptor (GLP-1R), an important clinical target. We use variants of the peptides GLP-1 and exendin-4 (Ex4) to explore the interplay between helical propensity near the agonist N terminus and the ability to bind to and activate the receptor. Cryo-EM analysis of a complex involving an Ex4 analog, the GLP-1R and G(s) heterotrimer revealed two receptor conformers with distinct modes of peptide-receptor engagement. Our functional and structural data, along with molecular dynamics (MD) simulations, suggest that receptor conformational dynamics associated with flexibility of the peptide N-terminal activation domain may be a key determinant of agonist efficacy. | |||
Structural and functional diversity among agonist-bound states of the GLP-1 receptor.,Cary BP, Deganutti G, Zhao P, Truong TT, Piper SJ, Liu X, Belousoff MJ, Danev R, Sexton PM, Wootten D, Gellman SH Nat Chem Biol. 2022 Mar;18(3):256-263. doi: 10.1038/s41589-021-00945-w. Epub 2021 , Dec 22. PMID:34937906<ref>PMID:34937906</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
<div class="pdbe-citations 7s1m" style="background-color:#fffaf0;"></div> | |||
==See Also== | |||
*[[Glucagon-like peptide receptor 3D structures|Glucagon-like peptide receptor 3D structures]] | |||
*[[Transducin 3D structures|Transducin 3D structures]] | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Homo sapiens]] | |||
[[Category: Lama glama]] | |||
[[Category: Large Structures]] | |||
[[Category: Synthetic construct]] | |||
[[Category: Cary BP]] | |||
[[Category: Gellman SH]] | |||
Latest revision as of 12:34, 9 October 2024
Ex4-D-Ala bound to the glucagon-like peptide-1 receptor/g protein complex (conformer 1)Ex4-D-Ala bound to the glucagon-like peptide-1 receptor/g protein complex (conformer 1)
Structural highlights
Publication Abstract from PubMedRecent advances in G-protein-coupled receptor (GPCR) structural elucidation have strengthened previous hypotheses that multidimensional signal propagation mediated by these receptors depends, in part, on their conformational mobility; however, the relationship between receptor function and static structures is inherently uncertain. Here, we examine the contribution of peptide agonist conformational plasticity to activation of the glucagon-like peptide 1 receptor (GLP-1R), an important clinical target. We use variants of the peptides GLP-1 and exendin-4 (Ex4) to explore the interplay between helical propensity near the agonist N terminus and the ability to bind to and activate the receptor. Cryo-EM analysis of a complex involving an Ex4 analog, the GLP-1R and G(s) heterotrimer revealed two receptor conformers with distinct modes of peptide-receptor engagement. Our functional and structural data, along with molecular dynamics (MD) simulations, suggest that receptor conformational dynamics associated with flexibility of the peptide N-terminal activation domain may be a key determinant of agonist efficacy. Structural and functional diversity among agonist-bound states of the GLP-1 receptor.,Cary BP, Deganutti G, Zhao P, Truong TT, Piper SJ, Liu X, Belousoff MJ, Danev R, Sexton PM, Wootten D, Gellman SH Nat Chem Biol. 2022 Mar;18(3):256-263. doi: 10.1038/s41589-021-00945-w. Epub 2021 , Dec 22. PMID:34937906[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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