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Crystallizing Thinking about the β2-Adrenergic Receptor

Department of Medicine (A.K.S., J.-P.S., R.J.L.), and Department of Biochemistry (A.K.S., J.-P.S., R.J.L.) and Howard Hughes Medical Institute (R.J.L.), Duke University Medical Center, Durham, North Carolina

Two recently determined crystal structures of the human β2-adrenergic receptor (β2AR) provide a long-awaited advance in the field of G protein-coupled receptor research. The β2AR is only the second member of this, the largest family of receptors encoded in the human genome, whose structure has been solved. It follows structures of rhodopsin that were determined previously. Here we set these developments in historical context, discuss the daunting challenges that have been overcome, and appraise what has and has not been learned.

Address correspondence to: Dr. Robert J. Lefkowitz, Box 3821, Duke University Medical Center, Durham, NC 27710. E-mail: lefko001{at}receptorbiol.duke.edu