Challenges for the structure determination of GPCR active conformation

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In order to understand the GPCR-mediated signal transduction mechanisms, it is essential to determine the GPCR structures in the active and inactive conformations. We published the structure of Histamine H1 receptor in complex with an inverse agonist doxepin. The structure revealed the reason why doxepin shows high affinities to aminergic receptors. We also published the structure of Adenosine A2a receptor in the inactive conformation. For crystallization, the receptor was stabilized in the inactive conformation by the binding of Fab fragment. The antibody that stabilizes the receptor in the active conformation was successfully obtained. This antibody will be useful for the determination of the Adenosine A2a receptor structure in the active conformation.