8x9u

Identification, structure and agonist design of an androgen membrane receptor

spinqualitylabelsall models 8x9u, resolution 2.88Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 8x9u is a 5 chain structure with sequence from Bos taurus, Homo sapiens, Rattus norvegicus and Synthetic construct. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: Electron Microscopy, Resolution 2.88Å Ligands: A1LU1 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function GBB1_RAT Guanine nucleotide-binding proteins (G proteins) are involved as a modulator or transducer in various transmembrane signaling systems. The beta and gamma chains are required for the GTPase activity, for replacement of GDP by GTP, and for G protein-effector interaction. Publication Abstract from PubMed Androgens, such as 5alpha-dihydrotestosterone (5alpha-DHT), regulate numerous functions by binding to nuclear androgen receptors (ARs) and potential unknown membrane receptors. Here, we report that the androgen 5alpha-DHT activates membrane receptor GPR133 in muscle cells, thereby increasing intracellular cyclic AMP (cAMP) levels and enhancing muscle strength. Further cryoelectron microscopy (cryo-EM) structural analysis of GPR133-Gs in complex with 5alpha-DHT or its derivative methenolone (MET) reveals the structural basis for androgen recognition. Notably, the presence of the "Phi(F/L)(2.64)-F(3.40)-W(6.53)" and the "F(7.42)xxN/D(7.46)" motifs, which recognize the hydrophobic steroid core and polar groups, respectively, are common in adhesion GPCRs (aGPCRs), suggesting that many aGPCRs may recognize different steroid hormones. Finally, we exploited in silico screening methods to identify a small molecule, AP503, which activates GPR133 and separates the beneficial muscle-strengthening effects from side effects mediated by AR. Thus, GPR133 represents an androgen membrane receptor that contributes to normal androgen physiology and has important therapeutic potentials. Identification, structure, and agonist design of an androgen membrane receptor.,Yang Z, Ping YQ, Wang MW, Zhang C, Zhou SH, Xi YT, Zhu KK, Ding W, Zhang QY, Song ZC, Zhao RJ, He ZL, Wang MX, Qi L, Ullmann C, Ricken A, Schoneberg T, Gan ZJ, Yu X, Xiao P, Yi F, Liebscher I, Sun JP Cell. 2025 Jan 23:S0092-8674(25)00035-2. doi: 10.1016/j.cell.2025.01.006. PMID:39884271 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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