Luirink J, High S, Wood H, Giner A, Tollervey D, Dobberstein B
European Molecular Biology Laboratory, Heidelberg, Germany.
Nature. 1992 Oct 22;359(6397):741-3. doi: 10.1038/359741a0.
Hydrophobic signal-sequences direct the transfer of secretory proteins across the inner membrane of prokaryotes and the endoplasmic reticulum membranes of eukaryotes. In mammalian cells, signal-sequences are recognized by the 54K protein (M(r) 54,000) of the signal recognition particle (SRP) which is believed to hold the nascent chain in a translocation-competent conformation until it contacts the endoplasmic reticulum membrane. The SRP consists of a 7S RNA and six different polypeptides. The 7S RNA and the 54K signal-sequence-binding protein (SRP54) of mammalian SRP exhibit strong sequence similarity to the 4.5S RNA and P48 protein (Ffh) of Escherichia coli which form a ribonucleoprotein particle. Depletion of 4.5S RNA or overproduction of P48 causes the accumulation of the beta-lactamase precursor, although not of other secretory proteins. Whether 4.5S RNA and P48 are part of an SRP-like complex with a role in protein export is controversial. Here we show that the P48/4.5S RNA ribonucleoprotein complex interacts specifically with the signal sequence of a nascent secretory protein and therefore is a signal recognition particle.
疏水信号序列指导分泌蛋白穿过原核生物的内膜以及真核生物的内质网膜。在哺乳动物细胞中，信号序列被信号识别颗粒（SRP）的54K蛋白（分子量54,000）识别，据信该蛋白会使新生链保持易位活性构象，直到它接触到内质网膜。SRP由7S RNA和六种不同的多肽组成。哺乳动物SRP的7S RNA和54K信号序列结合蛋白（SRP54）与大肠杆菌的4.5S RNA和P48蛋白（Ffh）具有很强的序列相似性，它们形成一种核糖核蛋白颗粒。4.5S RNA的缺失或P48的过量产生会导致β-内酰胺酶前体的积累，尽管其他分泌蛋白不会。4.5S RNA和P48是否作为一种类似SRP的复合物参与蛋白质输出存在争议。在这里，我们表明P48/4.5S RNA核糖核蛋白复合物与新生分泌蛋白的信号序列特异性相互作用，因此它是一种信号识别颗粒。
