8flu

Human PTH1R in complex with LA-PTH and GsHuman PTH1R in complex with LA-PTH and Gs

Structural highlights 8flu 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 2.76Å Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Publication Abstract from PubMed The parathyroid hormone (PTH) 1 receptor (PTH1R) is a G protein-coupled receptor (GPCR) that regulates skeletal development and calcium homeostasis. Here, we describe cryo-EM structures of the PTH1R in complex with fragments of the two hormones, PTH and PTH-related protein, the drug abaloparatide, as well as the engineered tool compounds, long-acting PTH (LA-PTH) and the truncated peptide, M-PTH(1-14). We found that the critical N terminus of each agonist engages the transmembrane bundle in a topologically similar fashion, reflecting similarities in measures of Galphas activation. The full-length peptides induce subtly different extracellular domain (ECD) orientations relative to the transmembrane domain. In the structure bound to M-PTH, the ECD is unresolved, demonstrating that the ECD is highly dynamic when unconstrained by a peptide. High resolutions enabled identification of water molecules near peptide and G protein binding sites. Our results illuminate the action of orthosteric agonists of the PTH1R. Molecular insights into peptide agonist engagement with the PTH receptor.,Cary BP, Gerrard EJ, Belousoff MJ, Fletcher MM, Jiang Y, Russell IC, Piper SJ, Wootten D, Sexton PM Structure. 2023 Jun 1;31(6):668-676.e5. doi: 10.1016/j.str.2023.04.002. Epub 2023 , May 5. PMID:37148874 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Transducin 3D structures

spinqualitylabelsall models 8flu, resolution 2.76Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image