Conformational changes in G-protein-coupled receptors -: the quest for functionally selective conformations is open
Conformational changes in G-protein-coupled receptors -: the quest for functionally selective conformations is open
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DOI：
10.1038/sj.bjp.0707615
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发表时间：
2008-03-01
影响因子：
7.3
通讯作者：
Lohse, M. J.
中科院分区：
文献类型：
--
作者：
Hoffmann, C.;Zuern, A.;Lohse, M. J.
G蛋白偶联受体(GPCRs)是最大的药物靶标家族之一。当激动剂结合时，受体经历构象重排，从而产生一种新的蛋白质构象，该构象又可以与效应蛋白相互作用。在过去的十年中，在证明发生不同构象变化方面取得了重大进展。目前，人们普遍认为不同的配体可以诱导不同的受体构象。然而，不同构象的性质或分子同一性仍然鲜为人知。了解潜在的功能选择性构象将有助于开发选择特定GPCR的特定构象的药物，这些构象耦合到特定的信号通路，并最终可能导致副作用减少。在这篇综述中，我们将总结生物物理方法的最新进展，这些方法已经导致了对GPCR激活过程中发生的构象变化的当前理解。
The G-protein-coupled receptors (GPCRs) represent one the largest families of drug targets. Upon agonist binding a receptor undergoes conformational rearrangements that lead to a novel protein conformation which in turn can interact with effector proteins. During the last decade significant progress has been made to prove that different conformational changes occur. Today it is mostly accepted that individual ligands can induce different receptor conformations. However, the nature or molecular identity of the different conformations is still ill-known. Knowledge of the potential functionally selective conformations will help to develop drugs that select specific conformations of a given GPCR which couple to specific signalling pathways and may, ultimately, lead to reduced side effects. In this review we will summarize recent progress in biophysical approaches that have led to the current understanding of conformational changes that occur during GPCR activation.