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Science. 2007 Nov 23;318(5854):1258-65. Epub 2007 Oct 25.

High-resolution crystal structure of an engineered human beta2-adrenergic G protein-coupled receptor.

Author information

1
Department of Molecular Biology, Scripps Research Institute, La Jolla, CA 92037, USA.

Abstract

Heterotrimeric guanine nucleotide-binding protein (G protein)-coupled receptors constitute the largest family of eukaryotic signal transduction proteins that communicate across the membrane. We report the crystal structure of a human beta2-adrenergic receptor-T4 lysozyme fusion protein bound to the partial inverse agonist carazolol at 2.4 angstrom resolution. The structure provides a high-resolution view of a human G protein-coupled receptor bound to a diffusible ligand. Ligand-binding site accessibility is enabled by the second extracellular loop, which is held out of the binding cavity by a pair of closely spaced disulfide bridges and a short helical segment within the loop. Cholesterol, a necessary component for crystallization, mediates an intriguing parallel association of receptor molecules in the crystal lattice. Although the location of carazolol in the beta2-adrenergic receptor is very similar to that of retinal in rhodopsin, structural differences in the ligand-binding site and other regions highlight the challenges in using rhodopsin as a template model for this large receptor family.

PMID:
17962520
PMCID:
PMC2583103
DOI:
10.1126/science.1150577
[Indexed for MEDLINE]
Free PMC Article

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