Kimata Naoki, Reeves Philip J, Smith Steven O
Department of Biochemistry and Cell Biology, Stony Brook University, Stony Brook, NY 11794-5215, United States.
School of Biological Sciences, University of Essex, Wivenhoe Park, Colchester, CO4 3SQ, United Kingdom.
J Magn Reson. 2015 Apr;253:111-8. doi: 10.1016/j.jmr.2014.12.014.
G protein-coupled receptors (GPCRs) span cell membranes with seven transmembrane helices and respond to a diverse array of extracellular signals. Crystal structures of GPCRs have provided key insights into the architecture of these receptors and the role of conserved residues. However, the question of how ligand binding induces the conformational changes that are essential for activation remains largely unanswered. Since the extracellular sequences and structures of GPCRs are not conserved between receptor subfamilies, it is likely that the initial molecular triggers for activation vary depending on the specific type of ligand and receptor. In this article, we describe NMR studies on the rhodopsin subfamily of GPCRs and propose a mechanism for how retinal isomerization switches the receptor to the active conformation. These results suggest a general approach for determining the triggers for activation in other GPCR subfamilies using NMR spectroscopy.
G蛋白偶联受体（GPCRs）通过七个跨膜螺旋跨越细胞膜，并对多种细胞外信号作出反应。GPCRs的晶体结构为这些受体的结构和保守残基的作用提供了关键见解。然而，配体结合如何诱导激活所必需的构象变化这一问题在很大程度上仍未得到解答。由于GPCRs的细胞外序列和结构在受体亚家族之间并不保守，激活的初始分子触发因素可能因配体和受体的具体类型而异。在本文中，我们描述了对GPCRs视紫红质亚家族的核磁共振研究，并提出了一种视黄醛异构化如何将受体切换到活性构象的机制。这些结果表明了一种使用核磁共振光谱法确定其他GPCR亚家族激活触发因素的通用方法。
