7d76 | pdb_00007d76

Cryo-EM structure of the beclomethasone-bound adhesion receptor GPR97-Go complex

spinqualitylabelsall models 7d76, resolution 3.10Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 7d76 is a 4 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: Electron Microscopy, Resolution 3.1Å Ligands: CLR, GXR, PLM, Y01 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Disease GNAO_HUMAN Early infantile epileptic encephalopathy. The disease is caused by mutations affecting the gene represented in this entry. The disease is caused by mutations affecting the gene represented in this entry. Function GNAO_HUMAN Guanine nucleotide-binding proteins (G proteins) are involved as modulators or transducers in various transmembrane signaling systems. The G(o) protein function is not clear. Stimulated by RGS14. Publication Abstract from PubMed Adhesion G-protein-coupled receptors (GPCRs) are a major family of GPCRs, but limited knowledge of their ligand regulation or structure is available(1-3). Here we report that glucocorticoid stress hormones activate adhesion G-protein-coupled receptor G3 (ADGRG3; also known as GPR97)(4-6), a prototypical adhesion GPCR. The cryo-electron microscopy structures of GPR97-G(o) complexes bound to the anti-inflammatory drug beclomethasone or the steroid hormone cortisol revealed that glucocorticoids bind to a pocket within the transmembrane domain. The steroidal core of glucocorticoids is packed against the 'toggle switch' residue W(6.53), which senses the binding of a ligand and induces activation of the receptor. Active GPR97 uses a quaternary core and HLY motif to fasten the seven-transmembrane bundle and to mediate G protein coupling. The cytoplasmic side of GPR97 has an open cavity, where all three intracellular loops interact with the G(o) protein, contributing to the high basal activity of GRP97. Palmitoylation at the cytosolic tail of the G(o) protein was found to be essential for efficient engagement with GPR97 but is not observed in other solved GPCR complex structures. Our work provides a structural basis for ligand binding to the seven-transmembrane domain of an adhesion GPCR and subsequent G protein coupling. Structures of the glucocorticoid-bound adhesion receptor GPR97-G(o) complex.,Ping YQ, Mao C, Xiao P, Zhao RJ, Jiang Y, Yang Z, An WT, Shen DD, Yang F, Zhang H, Qu C, Shen Q, Tian C, Li ZJ, Li S, Wang GY, Tao X, Wen X, Zhong YN, Yang J, Yi F, Yu X, Xu HE, Zhang Y, Sun JP Nature. 2021 Jan;589(7843):620-626. doi: 10.1038/s41586-020-03083-w. Epub 2021 , Jan 6. PMID:33408414 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Transducin 3D structures

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