Insights into signaling from the β2-adrenergic receptor structure
Insights into signaling from the β2-adrenergic receptor structure
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DOI：
10.1038/nchembio.97
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发表时间：
2008-07-01
影响因子：
14.8
通讯作者：
Bouvier, Michel
中科院分区：
文献类型：
--
作者：
Audet, Martin;Bouvier, Michel
G蛋白偶联受体家族有800多个成员，构成了参与信号转导的最大的膜蛋白群。直到去年年底，高分辨率的三维结构只能用于其中的一种——光受体视紫红质。最近，β 2-肾上腺素能受体的结构已被发现，它与视紫红质的结构有有趣的差异。对这些差异的分析提出了关于受体中扩散配体结合模式的重要问题，并允许制定关于将药物结合与特定信号反应联系起来的结构决定因素的可测试假设。由β 2-肾上腺素能受体晶体衍生的三维结构已被用于具有不同活性的配体的虚拟对接。这些配体的不同结合模式与其所报道的疗效相关，这表明有可能预测药物信号传导效果的结构决定因素。
With more than 800 members, the G protein - coupled receptor family constitutes the largest group of membrane proteins involved in signal transduction. Until the end of last year, high-resolution three-dimensional structures were available for only one of them - the light receptor rhodopsin. Recently the structure of the beta 2-adrenergic receptor has been obtained, and it revealed interesting differences with the structure of rhodopsin. Analyses of these differences raise important questions about the binding modes of diffusible ligands in the receptor and allow formulation of testable hypotheses about the structural determinants linking drug binding to specific signaling responses. The three-dimensional structure derived from the beta 2-adrenergic receptor crystal has been used to virtually dock ligands with distinct activities. The different binding modes of these ligands, which correlated with their reported efficacy profiles, suggest that it could be possible to predict the structural determinants of drug signaling efficacies.