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Crystal structure of oligomeric ?1-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 ?1-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.

SUBMITTER: Huang J

PROVIDER: S-EPMC3618578 | biostudies-literature | 2013 Apr

REPOSITORIES: biostudies-literature

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

Huang Jianyun J Chen Shuai S Zhang J Jillian JJ Huang Xin-Yun XY

Nature structural & molecular biology 20130224 4

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 tu ...[more]

PMID: 23435379

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