The complex behavior of GPCRs in response to natural or synthetic ligands and proteins can be attributed to the receptor’s structural plasticity manifested in multiple functionally distinct conformational states. We generated Xaperones (blue) which selectively recognize an active state of the human β2 adrenergic receptor (green). Such Xaperones that faithfully mimic the effects of G protein binding were used to obtain diffraction quality crystals and to solve the first structure of an active agonist-bound state of the human β2 adrenergic receptor.

Rasmussen SGF, Choi H-jung, Fung JJ, Pardon E, Casarosa P, Chae PS, Devree BT, Rosenbaum DM, Thian FS, Kobilka TS, Schnapp A, Konetzki I, Sunahara RK, Gellman SH, Pautsch A, Steyaert J, Weis WI & Kobilka BK (2011) Structure of a nanobody-stabilized active state of the ß2 adrenoceptor. Nature 469, 175–180.  See also N&V