Crystal structure of oligomeric β1-adrenergic G protein-coupled receptors in ligand-free basal state.

Publication Type:

Journal Article


Nat Struct Mol Biol, Volume 20, Issue 4, p.419-25 (2013)


Biopolymers, Dimerization, Disulfides, Ligands, Models, Molecular, Receptors, Adrenergic, beta-1, Receptors, G-Protein-Coupled


<p>G protein-coupled receptors (GPCRs) mediate transmembrane signaling. Before ligand binding, GPCRs exist in a basal state. Crystal structures of several GPCRs bound with antagonists or agonists have been solved. However, the crystal structure of the ligand-free basal state of a GPCR, the starting point of GPCR activation and function, had not yet been determined. Here we report the X-ray crystal structure of the ligand-free basal state of a GPCR in a lipid membrane-like environment. Oligomeric turkey β1-adrenergic receptors display two dimer interfaces. One interface involves the transmembrane domain (TM) 1, TM2, the C-terminal H8 and extracellular loop 1. The other interface engages residues from TM4, TM5, intracellular loop 2 and extracellular loop 2. Structural comparisons show that this ligand-free state is in an inactive conformation. This provides the structural basis of GPCR dimerization and oligomerization.</p>