Single-particle cryo-EM structural studies of the β2AR–Gs complex bound with a full agonist formoterol

Cryo-EM Structure of the Prostaglandin E Receptor EP4 Coupled to G Protein

“…Previous studies have successfully prepared stable GPCR-G protein complexes using GTP-free G protein to prevent the G protein from exchanging GTP and dissociating. Using these methods, the structures of b 1 and b 2 adrenergic receptors (b 1 AR and b 2 AR), adenosine A 2A receptor (A 2A R), and class A orphan GPCR (GPR52) have been determined to be class A GPCR-Gs complexes (García-Nafría et al, 2018;Lin et al, 2020;Rasmussen et al, 2011;Su et al, 2020;Zhang et al, 2020). Among these, the outward shift of the sixth transmembrane domain (TM6) of GPCR and insertion of the C-termi- nal helix of Gs into the GPCR are the structural features.…”

The Impact of the Secondary Binding Pocket on the Pharmacology of Class A GPCRs

“…Among them, 35 active aminergic GPCR structures have been published in the last 2 years ( Supplementary Table S2 ) ( Kooistra et al, 2021 ). These include 7 serotonin ( Kim et al, 2020 ; Peiyu Xu et al, 2021a ; Huang et al, 2021 ) (5-HTR), 15 dopamine ( Zhuang et al, 2021a ; Xiao et al, 2021 ; Zhuang et al, 2021b ; Yin et al, 2020 ; Peiyu Xu et al, 2021b ) (DR), 1 histamine ( Xia et al, 2021 ) (HR), 1 muscarinic ( Staus et al, 2020 ) (MR) and 11 adrenergic ( Lee et al, 2020 ; Fan Yang et al, 2021 ; Yuan et al, 2020 ; Su et al, 2020 ; Xinyu Xu et al, 2021 ; Zhang et al, 2020 ; Nagiri et al, 2021 ) (AR) receptor structures. Out of these complexes, 20 structures contain allosteric modulators but not obviously in the SBP, while 10 were co-crystallized with bitopic ligands bound both the OBP and the SBP.…”

“…Among them, 35 active aminergic GPCR structures have been published in the last 2 years (Supplementary Table S2) (Kooistra et al, 2021). These include 7 serotonin (Kim et al, 2020;Peiyu Xu et al, 2021a;Huang et al, 2021) (5-HTR), 15 dopamine (Zhuang et al, 2021a;Xiao et al, 2021;Zhuang et al, 2021b;Yin et al, 2020;Peiyu Xu et al, 2021b) (DR), 1 histamine (Xia et al, 2021) (HR), 1 muscarinic (Staus et al, 2020) (MR) and 11 adrenergic (Lee et al, 2020;Fan Yang et al, 2021;Yuan et al, 2020;Su et al, 2020;Xinyu Xu et al, 2021;Zhang et al, 2020; FIGURE 2 | (A) Schematic representation of the main allosteric sites in Class A GPCRs. The OBP, where the endogenous ligands bind to the receptor, is located between the extracellular allosteric site and the sodium binding site, deep in the crevice of the receptor formed by the transmembrane helixes.…”

Ligands of Adrenergic Receptors: A Structural Point of View

“…A remarkable case is dopamine receptor D 1 : no structure was reported before February 2021, and then 11 structures were released within two months [113,[133][134][135]. For adrenergic receptors, up to April 2021, a total of eight cryo-EM structures were published: one is arrestin-coupled β 1 AR and the others are G protein-coupled (four β 2 AR, G s [8,68,69]; one β 1 AR, G s [66]; two α 2B AR, G i and G o [52]).…”