Ensemble of G protein-coupled receptor active states.
Ensemble of G protein-coupled receptor active states.
复制标题
G蛋白偶联受体活性态的合奏。
DOI：
10.2174/092986712799320619
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发表时间：
2012
影响因子：
4.1
通讯作者：
Park PS
中科院分区：
文献类型：
--
作者：
Park PS
G蛋白偶联受体（GPCR）在细胞信号转导中起关键作用，并且是治疗的重要靶点。虽然这些受体已经被深入研究了相当长的一段时间，我们对它们的作用机制的理解仍然是不完整的。GPCR活性传统上是在双态模型的背景下看待的，其中受体处于单一非活性状态和单一活性状态之间的平衡。这个框架是太简单和限制性，以适应最近的观察这些受体，而不是指向的情况下，受体可以采用几种不同的活性构象substates具有不同的功能效果。结构和功能的证据，这一新兴的观点是在这次审查。这种新兴的观点合理化疾病状态和药物发现的影响也进行了讨论。
G protein-coupled receptors (GPCRs) play critical roles in cellular signal transduction and are important targets for therapeutics. Although these receptors have been intensely studied for quite some time, our understanding about their mechanism of action is still incomplete. GPCR activity has traditionally been viewed within the context of two-state models where the receptor is in equilibrium between a single inactive state and a single active state. This framework is too simple and restrictive to accommodate more recent observations made on these receptors, which instead point to a situation where the receptor can adopt several different active conformational substates with distinct functional effects. Structural and functional evidence for this emerging view is presented in this review. Implications of this emerging view in rationalizing diseased states and in drug discovery are also discussed.