Bartuzi Damian, Kaczor Agnieszka A, Matosiuk Dariusz
Department of Synthesis and Chemical Technology of Pharmaceutical Substances with Computer Modelling Lab, Medical University of Lublin, 4A Chodźki Str., Lublin PL20093, Poland.
School of Pharmacy, University of Eastern Finland, Yliopistonranta 1, P.O. Box 1627, Kuopio FI-70211, Finland.
Molecules. 2017 Jul 15;22(7):1188. doi: 10.3390/molecules22071188.
In recent years, our understanding of function of G protein-coupled receptors (GPCRs) has changed from a picture of simple signal relays, transmitting only a particular signal to a particular G protein heterotrimer, to versatile machines, capable of various responses to different stimuli and being modulated by various factors. Some recent reports provide not only the data on ligands/modulators and resultant signals induced by them, but also deeper insights into exact pathways of signal migration and mechanisms of signal transmission through receptor structure. Combination of these computational and experimental data sheds more light on underlying mechanisms of signal transmission and signaling bias in GPCRs. In this review we focus on available clues on allosteric pathways responsible for complex signal processing within GPCRs structures, with particular emphasis on linking compatible in silico- and in vitro-derived data on the most probable allosteric connections.
近年来，我们对G蛋白偶联受体（GPCRs）功能的理解已从仅向特定G蛋白异源三聚体传递特定信号的简单信号中继模式，转变为能够对不同刺激产生各种反应并受多种因素调节的多功能机制。最近的一些报告不仅提供了关于配体/调节剂及其诱导的信号的数据，还对信号迁移的精确途径以及通过受体结构进行信号传递的机制有了更深入的见解。这些计算数据和实验数据的结合，为GPCRs中信号传递和信号偏向的潜在机制提供了更多线索。在本综述中，我们重点关注GPCRs结构内负责复杂信号处理的变构途径的现有线索，特别强调将计算机模拟和体外实验得出的关于最可能变构连接的兼容数据联系起来。
