Challenges for the structure determination of GPCR active conformation

为了了解GPCR介导的信号转导机制，有必要确定活性构象和非活性构象中的GPCR结构。我们发表了组胺H1受体与逆激动剂多虑平复合物的结构。这种结构揭示了多肽对胺能受体具有高亲和力的原因。我们还公布了腺苷A2a受体在非活性构象中的结构。在结晶过程中，受体通过与Fab片段的结合稳定在非活性构象上。成功地获得了稳定受体活性构象的抗体。该抗体可用于测定活性构象中的腺苷A2a受体结构。

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.