7s1m

Ex4-D-Ala bound to the glucagon-like peptide-1 receptor/g protein complex (conformer 1)

spinqualitylabelsall models 7s1m, resolution 2.41Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 7s1m is a 6 chain structure with sequence from Homo sapiens, Lama glama and Synthetic construct. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: Electron Microscopy, Resolution 2.41Å Ligands: DAL Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT 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 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Glucagon-like peptide receptor 3D structures Transducin 3D structures

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