title: Crystal structure of oligomeric β1-adrenergic G protein-coupled receptors in ligand-free basal state.
abstract: 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.
authors: Department of Physiology and Biophysics, Cornell University Weill Medical College, New York, New York, USA.
authors: Jianyun
authors: J
authors: Huang
authors: Shuai
authors: S
authors: Chen
authors: J Jillian
authors: JJ
authors: Zhang
authors: Xin-Yun
authors: XY
authors: Huang
mesh_terms: D001704:Biopolymers; D019281:Dimerization; D004220:Disulfides / Q000737:chemistry; D008024:Ligands; D008958:Models, Molecular; D018342:Receptors, Adrenergic, beta-1 / Q000737:chemistry*; D043562:Receptors, G-Protein-Coupled / Q000737:chemistry*
chemical_list: D001704:Biopolymers; D004220:Disulfides; D008024:Ligands; D018342:Receptors, Adrenergic, beta-1; D043562:Receptors, G-Protein-Coupled