7D76

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

Summary for 7D76

• Entry DOI: 10.2210/pdb7d76/pdb
• EMDB information: 30602
• Descriptor: Guanine nucleotide-binding protein G(o) subunit alpha, Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1, Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2, ... (8 entities in total)
• Functional Keywords: gpcr, gpr97, complex, adhesion g protein-coupled receptor, membrane protein
• Biological source: Homo sapiens; More
• Total number of polymer chains: 4
• Total formula weight: 136599.19

Authors

Ping, Y.,Mao, C.,Xiao, P.,Zhao, R.,Jiang, Y.,Yang, Z.,An, W.,Shen, D.,Yang, F.,Zhang, H.,Qu, C.,Shen, Q.,Tian, C.,Li, Z.,Li, S.,Wang, G.,Tao, X.,Wen, X.,Zhong, Y.,Yang, J.,Yi, F.,Yu, X.,Xu, E.,Zhang, Y.,Sun, J. (deposition date: 2020-10-03, release date: 2021-02-03, Last modification date: 2024-10-30)

Primary citation

Ping, Y.Q.,Mao, C.,Xiao, P.,Zhao, R.J.,Jiang, Y.,Yang, Z.,An, W.T.,Shen, D.D.,Yang, F.,Zhang, H.,Qu, C.,Shen, Q.,Tian, C.,Li, Z.J.,Li, S.,Wang, G.Y.,Tao, X.,Wen, X.,Zhong, Y.N.,Yang, J.,Yi, F.,Yu, X.,Xu, H.E.,Zhang, Y.,Sun, J.P.
Structures of the glucocorticoid-bound adhesion receptor GPR97-G o complex.
Nature, 589:620-626, 2021

PubMed Abstract: Adhesion G-protein-coupled receptors (GPCRs) are a major family of GPCRs, but limited knowledge of their ligand regulation or structure is available. Here we report that glucocorticoid stress hormones activate adhesion G-protein-coupled receptor G3 (ADGRG3; also known as GPR97), a prototypical adhesion GPCR. The cryo-electron microscopy structures of GPR97-G 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, 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 protein, contributing to the high basal activity of GRP97. Palmitoylation at the cytosolic tail of the G 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.

PubMed: 33408414
DOI: 10.1038/s41586-020-03083-w

Experimental method

ELECTRON MICROSCOPY (3.1 Å)