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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Mapping allosteric connections from the receptor to the nucleotide-binding pocket of heterotrimeric G proteins
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Mapping allosteric connections from the receptor to the nucleotide-binding pocket of heterotrimeric G proteins

机译：映射从受体到异源三聚体G蛋白的核苷酸结合口袋的变构连接

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摘要

Heterotrimeric G proteins function as molecular relays that mediate signal transduction from heptahelical receptors in the cell membrane to intracellular effector proteins. Crystallographic studies have demonstrated that guanine nucleotide exchange on the Gα subunit causes specific conformational changes in three key "switch" regions of the protein, which regulate binding to Gβγ subunits, receptors, and effector proteins. In the present study, nitroxide side chains were introduced at sites within the switch Ⅰ region of Gαi to explore the structure and dynamics of this region throughout the G protein cycle. EPR spectra obtained for each of the Gα(GDP), Gα(GDP)βγ heterotrimer and Gα(GTPγS) conformations are consistent with the local environment observed in the corresponding crystal structures. Binding of the heterotrimer to activated rhodopsin to form the nucleotide-free (empty) complex, for which there is no crystal structure, causes prominent changes relative to the heterotrimer in the structure of switch Ⅰ and contiguous sequences. The data identify a putative pathway of allosteric changes triggered by receptor binding and, together with previously published data, suggest elements of a mechanism for receptor-catalyzed nucleotide exchange.
机译：异三聚体G蛋白起分子中继的作用，介导信号从细胞膜中的七螺旋受体传导至细胞内效应蛋白。晶体学研究表明，Gα亚基上的鸟嘌呤核苷酸交换在蛋白质的三个关键“开关”区域中引起特定的构象变化，从而调节与Gβγ亚基，受体和效应蛋白的结合。在本研究中，在Gαi的Ⅰ开关区域内的部位引入了氮氧化物侧链，以探索该区域在整个G蛋白循环中的结构和动力学。对Gα（GDP），Gα（GDP）βγ异三聚体和Gα（GTPγS）构象分别获得的EPR光谱与在相应晶体结构中观察到的局部环境一致。异源三聚体与活化的视紫红质的结合形成无核苷酸（空）的复合物，该复合物没有晶体结构，相对于异源三聚体在开关Ⅰ和连续序列的结构上引起显着变化。数据确定了由受体结合​​触发的变构变化的推定途径，并且与先前公开的数据一起提示了受体催化的核苷酸交换机制的要素。

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