Conformational Transitions and the Activation of Heterotrimeric G Proteins by G Protein-Coupled Receptors
Conformational Transitions and the Activation of Heterotrimeric G Proteins by G Protein-Coupled Receptors
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DOI：
10.1021/acsptsci.9b00054
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发表时间：
2019-08-09
影响因子：
--
通讯作者：
Furness, Sebastian George Barton
中科院分区：
文献类型：
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作者：
Draper-Joyce, Christopher;Furness, Sebastian George Barton
G蛋白偶联受体（GPCR）是治疗药物的特别有吸引力的靶标。这是因为它们几乎参与了生理学的几乎所有方面，在许多病理生理过程中，由于细胞表面的位置，它们是可探讨的，并且可以表现出高质感的药理学。尽管新药的发展不需要特定靶标的活动机理的分子细节，但在这些细节中，对GPCR领域的兴趣越来越高。在某种程度上，这是因为人们认识到，特定目标的差异活动可能是通过操纵功效或通过差异耦合（信号偏差）来利用药物活动的一种方式。为此，在过去的几年中，有许多出版物专门试图解决分子反应途径的一个或多个方面，从而导致GPCR激活异构三聚体G蛋白。
G protein-coupled receptors (GPCRs) are particularly attractive targets for therapeutic pharmaceuticals. This is because they are involved in almost all facets of physiology, in many pathophysiological processes, they are tractable due to their cell surface location, and can exhibit highly textured pharmacology. While the development of new drugs does not require the molecular details of the mechanism of activity for a particular target, there has been increasing interest in the GPCR field in these details. In part, this has come with the recognition that differential activity at a particular target might be a way in which to leverage drug activity, either through manipulation of efficacy or through differential coupling (signaling bias). To this end, the past few years have seen a number of publications that have specifically attempted to address one or more aspects of the molecular reaction pathway, leading to activation of heterotrimeric G proteins by GPCRs.