7ra3

cryo-EM of human Gastric inhibitory polypeptide receptor GIPR bound to GIP

spinqualitylabelsall models 7ra3, resolution 3.24Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 7ra3 is a 7 chain structure with sequence from Homo sapiens, Lama glama and Mus musculus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: Electron Microscopy, Resolution 3.24Å Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT 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 SignificanceTirzepatide is a dual agonist of the glucose-dependent insulinotropic polypeptide receptor (GIPR) and the glucagon-like peptide-1 receptor (GLP-1R), which are incretin receptors that regulate carbohydrate metabolism. This investigational agent has proven superior to selective GLP-1R agonists in clinical trials in subjects with type 2 diabetes mellitus. Intriguingly, although tirzepatide closely resembles native GIP in how it activates the GIPR, it differs markedly from GLP-1 in its activation of the GLP-1R, resulting in less agonist-induced receptor desensitization. We report how cryogenic electron microscopy and molecular dynamics simulations inform the structural basis for the unique pharmacology of tirzepatide. These studies reveal the extent to which fatty acid modification, combined with amino acid sequence, determines the mode of action of a multireceptor agonist. Structural determinants of dual incretin receptor agonism by tirzepatide.,Sun B, Willard FS, Feng D, Alsina-Fernandez J, Chen Q, Vieth M, Ho JD, Showalter AD, Stutsman C, Ding L, Suter TM, Dunbar JD, Carpenter JW, Mohammed FA, Aihara E, Brown RA, Bueno AB, Emmerson PJ, Moyers JS, Kobilka TS, Coghlan MP, Kobilka BK, Sloop KW Proc Natl Acad Sci U S A. 2022 Mar 29;119(13):e2116506119. doi: , 10.1073/pnas.2116506119. Epub 2022 Mar 25. PMID:35333651 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Transducin 3D structures

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