High-resolution crystal structure of an engineered human beta2-adrenergic G protein-coupled receptor by Cherezov Vadim, Rosenbaum Daniel M, Hanson Michael A, Rasmussen Søren G F, Thian Foon Sun, Kobilka Tong Sun, Choi Hee-Jung, Kuhn Peter, Weis William I, Kobilka Brian K, Stevens Raymond C in Science (New York, N.Y.) (2007). PubMed

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.

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