7w40

Cryo-EM Structure of Human Gastrin Releasing Peptide Receptor in complex with the agonist Bombesin (6-14) [D-Phe6, beta-Ala11, Phe13, Nle14] and Gq heterotrimers

spinqualitylabelsall models 7w40, resolution 3.00Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 7w40 is a 6 chain structure with sequence from Escherichia coli, Homo sapiens and Synthetic construct. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: Electron Microscopy, Resolution 3Å Ligands: BAL, DPN, NLN Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Publication Abstract from PubMed Gastrin releasing peptide receptor (GRPR), a member of the bombesin (BBN) G protein-coupled receptors, is aberrantly overexpressed in several malignant tumors, including those of the breast, prostate, pancreas, lung, and central nervous system. Additionally, it also mediates non-histaminergic itch and pathological itch conditions in mice. Thus, GRPR could be an attractive target for cancer and itch therapy. Here, we report the inactive state crystal structure of human GRPR in complex with the non-peptide antagonist PD176252, as well as two active state cryo-electron microscopy (cryo-EM) structures of GRPR bound to the endogenous peptide agonist gastrin-releasing peptide and the synthetic BBN analog [D-Phe(6), beta-Ala(11), Phe(13), Nle(14)] Bn (6-14), in complex with G(q) heterotrimers. These structures revealed the molecular mechanisms for the ligand binding, receptor activation, and G(q) proteins signaling of GRPR, which are expected to accelerate the structure-based design of GRPR antagonists and agonists for the treatments of cancer and pruritus. Structures of human gastrin-releasing peptide receptors bound to antagonist and agonist for cancer and itch therapy.,Peng S, Zhan Y, Zhang D, Ren L, Chen A, Chen ZF, Zhang H Proc Natl Acad Sci U S A. 2023 Feb 7;120(6):e2216230120. doi: , 10.1073/pnas.2216230120. Epub 2023 Feb 1. PMID:36724251 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Transducin 3D structures

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