Regulation by the ribosome of the GTPase of the signal-recognition particle during protein targeting
Regulation by the ribosome of the GTPase of the signal-recognition particle during protein targeting
复制标题
DOI：
10.1038/381248a0
复制
发表时间：
1996-05-16
期刊：
影响因子：
64.8
通讯作者：
Dobberstein, B
中科院分区：
文献类型：
--
作者：
Bacher, G;Lutcke, H;Dobberstein, B
信号识别颗粒(SRP)对于许多分泌和膜蛋白定位于内质网(ER)起着重要作用。靶向由三个GTP酶调控，即SRP的54K亚基(SRP54)和SRP受体的α和β亚基(1)。当核糖体出现信号序列时，SRP与其相互作用，并通过与SRP受体结合将产生的复合体靶向内质网膜。随后，SRP将信号序列释放到移位信道(2，3)。在这里，我们使用核糖体与新生肽链的复合体，SRP及其受体，来研究GTP与SRP54的结合和GTP的水解。我们的发现表明，一个核糖体成分促进了GTP与SRP的SRP54亚基的结合，GTP结合的SRP54是SRP与其ER膜上的受体高亲和力所必需的。这种相互作用导致SRP信号序列的释放，新生的多肽链插入易位通道，以及GTP水解。核糖体的贡献以前没有被发现，因为在分析中只使用了合成信号肽(4)。
THE signal-recognition particle (SRP) is important for the targeting of many secretory and membrane proteins to the endoplasmic reticulum (ER). Targeting is regulated by three GTPases, the 54K subunit of SRP (SRP54), and the alpha- and beta-subunits of the SRP receptor(1). When a signal sequence emerges from the ribosome, SRP interacts with it and targets the resulting complex to the ER membrane by binding to the SRP receptor. Subsequently, SRP releases the signal sequence into the translocation channel(2,3). Here we use a complex of a ribosome with a nascent peptide chain, the SRP and its receptor, to investigate GTP binding to SRP54, and GTP hydrolysis. Our findings indicate that a ribosomal component promotes GTP binding to the SRP54 subunit of SRP, GTP-bound SRP54 is essential for high-affinity interaction between SRP and its receptor in the ER membrane. This interaction induces the release of the signal sequence from SRP, the insertion of the nascent polypeptide chain into the translocation channel, and GTP hydrolysis. The contribution of the ribosome had previously escaped detection because only synthetic signal peptides were used in the analysis(4).