Miller J D, Bernstein H D, Walter P
Department of Biochemistry and Biophysics, University of California Medical School, San Francisco 94143-0448.
Nature. 1994 Feb 17;367(6464):657-9. doi: 10.1038/367657a0.
The mechanism of protein translocation across the endoplasmic reticulum membrane of eukaryotic cells and the plasma membrane of prokaryotic cells are thought to be evolutionarily related. Protein targeting to the eukaryotic translocation apparatus is mediated by the signal recognition particle (SRP), a cytosolic ribonucleoprotein, and the SRP receptor, an endoplasmic reticulum membrane protein. During targeting, the 54K SRP subunit (M(r) 54,000; SRP54), a GTP-binding protein, binds to signal sequences and then interacts with the alpha-subunit of the SRP receptor (SR alpha), another GTP-binding protein. Two proteins from Escherichia coli, Ffh and FTsY, structurally resemble SRP54 and SR alpha. Like SRP54, Ffh is a subunit of a cytosolic ribonucleoprotein that also contains the E. coli 4.5S RNA. Although there is genetic and biochemical evidence that the E. coli Ffh/4.5S ribonucleoprotein has an SRP-like function, there is no evidence for an SR alpha-like role for FtsY. Here we show that the Ffh/4.5S ribonucleoprotein binds tightly to FtsY in a GTP-dependent manner. This interaction results in the stimulation of GTP hydrolysis which can be inhibited by synthetic signal peptides. These properties mimic those of mammalian SRP and its receptor, suggesting that the E. coli Ffh/4.5S ribonucleoprotein and FtsY have functions in protein targeting that are similar to those of their mammalian counterparts.
真核细胞内质网膜和原核细胞质膜上蛋白质转运的机制被认为在进化上是相关的。蛋白质靶向真核转运装置是由信号识别颗粒（SRP）介导的，SRP是一种胞质核糖核蛋白，以及SRP受体，一种内质网膜蛋白。在靶向过程中，54K SRP亚基（分子量54,000；SRP54），一种GTP结合蛋白，与信号序列结合，然后与SRP受体的α亚基（SRα）相互作用，SRα也是一种GTP结合蛋白。来自大肠杆菌的两种蛋白质Ffh和FtsY在结构上类似于SRP54和SRα。与SRP54一样，Ffh是一种胞质核糖核蛋白的亚基，该核糖核蛋白还包含大肠杆菌4.5S RNA。尽管有遗传和生化证据表明大肠杆菌Ffh/4.5S核糖核蛋白具有类似SRP的功能，但没有证据表明FtsY具有类似SRα的作用。在这里，我们表明Ffh/4.5S核糖核蛋白以GTP依赖的方式与FtsY紧密结合。这种相互作用导致GTP水解的刺激，而合成信号肽可以抑制这种刺激。这些特性模仿了哺乳动物SRP及其受体的特性，表明大肠杆菌Ffh/4.5S核糖核蛋白和FtsY在蛋白质靶向中的功能与其哺乳动物对应物相似。
