Complexes between photoactivated rhodopsin and transducin: progress and questions.
Complexes between photoactivated rhodopsin and transducin: progress and questions.
复制标题
DOI：
10.1042/bj20100270
复制
发表时间：
2010-04-28
期刊：
影响因子：
--
通讯作者：
Palczewski K
中科院分区：
文献类型：
--
作者：
Jastrzebska B;Tsybovsky Y;Palczewski K
GPCR（G蛋白偶联受体）的激活导致构象变化，最终启动信号转导。活化的GPCR与异源三聚体G蛋白瞬时联合收割机结合并活化，导致G蛋白α亚基上GDP的GTP置换。G蛋白α亚基上的生产性GDP/GTP交换所必需的详细结构变化和GPCR-G蛋白复合物本身的结构都尚未阐明。然而，瞬时GPCR-G-蛋白复合物可以通过核苷酸耗尽被捕获，产生可以被分离的空核苷酸G-蛋白-GPCR复合物。早期的生物化学研究表明，G蛋白和激活的受体之间只形成复合物，而最近的结果表明，G蛋白可以结合到受体的预激活状态，甚至短暂耦合到非激活的受体，以促进对刺激的快速反应。生理相关的，构象均匀的GPCR-G-蛋白复合物的有效和可再现的形成是设计来解决这些可能性的结构研究的先决条件。
Activation of GPCRs (G-protein-coupled receptors) leads to conformational changes that ultimately initiate signal transduction. Activated GPCRs transiently combine with and activate heterotrimeric G-proteins resulting in GTP replacement of GDP on the G-protein α subunit. Both the detailed structural changes essential for productive GDP/GTP exchange on the G-protein α subunit and the structure of the GPCR–G-protein complex itself have yet to be elucidated. Nevertheless, transient GPCR–G-protein complexes can be trapped by nucleotide depletion, yielding an empty-nucleotide G-protein–GPCR complex that can be isolated. Whereas early biochemical studies indicated formation of a complex between G-protein and activated receptor only, more recent results suggest that G-protein can bind to pre-activated states of receptor or even couple transiently to non-activated receptor to facilitate rapid responses to stimuli. Efficient and reproducible formation of physiologically relevant, conformationally homogenous GPCR–G-protein complexes is a prerequisite for structural studies designed to address these possibilities.