Recent Progress in Understanding of Structure, Ligand Interactions and the Mechanism of Activation of the β 2-Adrenergic Receptor

M.      Kolinski; A.      Plazinska; K.      Jozwiak

Abstract

The understanding of β2-adrenergic receptor (β2AR) interactions with ligands as well as the mechanism of receptor activation changed radically from 2007, when the first crystallographic structure of the receptor was reported. Since then numerous crystallographic studies described interactions with all main classes of β2AR ligands and with G proteins, which provided a great insight into the molecular structure of the receptor. However, molecular mechanisms of receptor activations remain to be determined. Functional research supported the concept of ligand - directed signaling at β-adrenoceptors. Agonist can activate alternative signaling pathways with different capacities and trigger cellular effects. It indicates that agonists nominally belonging to the same class may bind to and/or stabilize different active conformations of the receptor which are selectively recognized by signaling proteins in the allosteric manner.

Keywords: β2AR, biased agonism, crystal structure, GPCRs, molecular switches, receptor activation, β-adrenoceptors, signaling pathways, allosteric manner, peptides, or proteins