背景：已显示膜胆固醇失调会改变腺苷A2A受体（A2AR）的活性，G蛋白偶联受体，从而将胆固醇水平与老年痴呆症和帕金森氏症等疾病联系起来。有限数量的A2AR晶体结构显示受体与胆固醇相互作用，这样的分子模拟通常用于预测胆固醇相互作用位点。
方法：这里，我们使用实验方法来确定全长胆固醇共有基序(CCM)中氨基酸侧链之间是否存在特异性相互作用,野生型人类A2AR，胆固醇通过测试突变对功能后果的影响来调节受体的活性，包括配体结合，G蛋白偶联,以及环状AMP的下游激活。
结论：我们的数据，采取与以前发表的研究，支持胆固醇和CCM之间的受体状态依赖性结合模型，其中胆固醇促进G蛋白偶联和A2AR的下游信号传导。
BACKGROUND: Membrane cholesterol dysregulation has been shown to alter the activity of the adenosine A2A receptor (A2AR), a G protein-coupled receptor, thereby implicating cholesterol levels in diseases such as Alzheimer\'s and Parkinson\'s. A limited number of A2AR crystal structures show the receptor interacting with cholesterol, as such molecular simulations are often used to predict cholesterol interaction sites.
METHODS: Here, we use experimental methods to determine whether a specific interaction between amino acid side chains in the cholesterol
consensus motif (CCM) of full length, wild-type human A2AR, and cholesterol modulates activity of the receptor by testing the effects of mutational changes on functional consequences, including ligand binding, G protein coupling, and downstream activation of cyclic AMP.
CONCLUSIONS: Our data, taken with previously published studies, support a model of receptor state-dependent binding between cholesterol and the CCM, whereby cholesterol facilitates both G protein coupling and downstream signaling of A2AR.
