PDBsum entry 7d76

Membrane protein

PDB id: 7d76

Contents

Protein chains

215 a.a.

338 a.a.

56 a.a.

265 a.a.

Ligands

PLM ×3

Y01

GXR

CLR ×2

PDB id:

7d76

Name:

Membrane protein

Title:

Cryo-em structure of the beclomethasone-bound adhesion receptor gpr97- go complex

Structure:

Guanine nucleotide-binding protein g(o) subunit alpha. Chain: a. Engineered: yes. Guanine nucleotide-binding protein g(i)/g(s)/g(t) subunit beta-1. Chain: b. Synonym: transducin beta chain 1. Engineered: yes. Guanine nucleotide-binding protein g(i)/g(s)/g(o) subunit

Source:

Homo sapiens. Organism_taxid: 9606. Gene: gnao1. Expressed in: spodoptera frugiperda. Expression_system_taxid: 7108. Expression_system_cell: sf9. Human. Gene: gnb1. Gene: gng2.

Authors:

Y.Ping,C.Mao,P.Xiao,R.Zhao,Y.Jiang,Z.Yang,W.An,D.Shen,F.Yang,H.Zhang, C.Qu,Q.Shen,C.Tian,Z.Li,S.Li,G.Wang,X.Tao,X.Wen,Y.Zhong,J.Yang,F.Yi, X.Yu,E.Xu,Y.Zhang,J.Sun

Key ref:

Y.Q.Ping et al. (2021). Structures of the glucocorticoid-bound adhesion receptor GPR97-G_o complex. Nature, 589, 620-626. PubMed id: 33408414 DOI: 10.1038/s41586-020-03083-w

Date:

03-Oct-20 Release date: 03-Feb-21

Protein chain

P09471  (GNAO_HUMAN) -  Guanine nucleotide-binding protein G(o) subunit alpha from Homo sapiens

Seq: 354 a.a.

Struc: 215 a.a.*

Protein chain

P62873  (GBB1_HUMAN) -  Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1 from Homo sapiens

Seq: 340 a.a.

Struc: 338 a.a.

Protein chain

P59768  (GBG2_HUMAN) -  Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2 from Homo sapiens

Seq: 71 a.a.

Struc: 56 a.a.

Protein chain

Q86Y34  (AGRG3_HUMAN) -  Adhesion G protein-coupled receptor G3 from Homo sapiens

Seq: 549 a.a.

Struc: 265 a.a.

* PDB and UniProt seqs differ at 6 residue positions (black crosses)

Enzyme reactions

• Enzyme class: Chain A: E.C.3.6.5.- - ?????

DOI no: 10.1038/s41586-020-03083-w

Nature 589:620-626 (2021)

PubMed id: 33408414

Structures of the glucocorticoid-bound adhesion receptor GPR97-G_o complex.

Y.Q.Ping, C.Mao, P.Xiao, R.J.Zhao, Y.Jiang, Z.Yang, W.T.An, D.D.Shen, F.Yang, H.Zhang, C.Qu, Q.Shen, C.Tian, Z.J.Li, S.Li, G.Y.Wang, X.Tao, X.Wen, Y.N.Zhong, J.Yang, F.Yi, X.Yu, H.E.Xu, Y.Zhang, J.P.Sun.

ABSTRACT

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.