High-resolution crystal structure of an engineered human beta2-adrenergic G protein-coupled receptor
Research output: Contribution to journal › Journal article › Research › peer-review
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.
Original language | English |
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Journal | Science (New York, N.Y.) |
Volume | 318 |
Issue number | 5854 |
Pages (from-to) | 1258-65 |
Number of pages | 8 |
ISSN | 0036-8075 |
DOIs | |
Publication status | Published - 23 Nov 2007 |
- Bacteriophage T4, Binding Sites, Cell Membrane, Cholesterol, Crystallization, Crystallography, X-Ray, Drug Inverse Agonism, Humans, Ligands, Models, Molecular, Muramidase, Propanolamines, Protein Conformation, Protein Folding, Protein Structure, Secondary, Receptors, Adrenergic, beta-2, Recombinant Fusion Proteins, Rhodopsin, Static Electricity
Research areas
ID: 120588695