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Two Crystal Structures of the beta2‐Adrenergic Receptor
Author(s) -
Weis William I.
Publication year - 2009
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.23.1_supplement.330.2
Subject(s) - g protein coupled receptor , receptor , chemistry , lysozyme , ligand (biochemistry) , inverse agonist , intracellular , signal transduction , microbiology and biotechnology , biophysics , biochemistry , agonist , biology
G protein coupled receptors (GPCRs) constitute the largest family of membrane proteins in the human genome, and are responsible for the majority of signal transduction events involving hormones and neurotransmitters across the cell membrane. GPCRs that bind to diffusible ligands have low natural abundance, are relatively unstable in detergents, and display basal G protein activation even in the absence of ligands. To overcome these problems two approaches were taken to obtain crystal structures of the β 2 ‐adrenergic receptor (β 2 AR), a well‐characterized GPCR that binds catecholamine hormones. The receptor was bound to the partial inverse agonist carazolol and co‐crystallized with a Fab made to a three‐dimensional epitope formed by the third intracellular loop (ICL3), or by replacement of ICL3 with T4 lysozyme. Small crystals were obtained in lipid bicelles (β 2 AR‐Fab) or lipidic cubic phase (β 2 AR‐T4 lysozyme), and diffraction data were obtained using microfocus technology. The structures provide insights into the basal activity of the receptor, the structural features that enable binding of diffusible ligands, and the coupling between ligand binding and G‐protein activation.