GTP-BINDING AND HYDROLYSIS BY THE SIGNAL RECOGNITION PARTICLE DURING INITIATION OF PROTEIN TRANSLOCATION
GTP-BINDING AND HYDROLYSIS BY THE SIGNAL RECOGNITION PARTICLE DURING INITIATION OF PROTEIN TRANSLOCATION
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DOI：
10.1038/366351a0
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发表时间：
1993-11-25
期刊：
影响因子：
64.8
通讯作者：
WALTER, P
中科院分区：
文献类型：
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作者：
MILLER, JD;WILHELM, H;WALTER, P
信号识别颗粒（SRP）由一个RNA和六个蛋白质亚基组成1，2。54 K亚基的N-末端结构域含有推定的GTP结合位点，而C-末端结构域结合信号序列和SRP RNA 3 -7。当信号序列从核糖体出现时，SRP与信号序列的结合产生含有新生多肽链、翻译核糖体和SRP 8的胞质靶向复合物。由于与SRP受体相互作用，该复合物被导向内质网膜9 -11，SRP受体是一种由两个亚基SR α和SR β组成的膜蛋白，每个亚基还含有GTP结合结构域12，13。在GTP的存在下，SRP受体与SRP的结合导致后者与信号序列和核糖体解离13，14。然后GTP被水解，使得SRP可以从SRP受体释放并返回到胞质溶胶15。在这里，我们表明，SRP（SRP 54）的54 K亚基（M（r）54，000）是一种GTP结合蛋白，通过信号序列稳定在无核苷酸状态，并且SRP受体既增加了SRP 54对GTP的亲和力，又激活了其GTP酶。我们建议，核苷酸介导的构象变化在SRP 54调节信号序列的释放和核糖体在内质网的对接。
THE signal recognition particle (SRP) consists of one RNA and six protein subunits1,2. The N-terminal domain of the 54K subunit contains a putative GTP-binding site, whereas the C-terminal domain binds signal sequences and SRP RNA3-7. Binding of SRP to the signal sequence as it emerges from the ribosome creates a cytosolic targeting complex containing the nascent polypeptide chain, the translating ribosome, and SRP8. This complex is directed to the endoplasmic reticulum membrane as a result of its interaction with the SRP receptor9-11, a membrane protein composed of two subunits, SRalpha and SRbeta, each of which also contains a GTP-binding domain12,13. In the presence of GTP, SRP receptor binding to SRP causes the latter to dissociate from both the signal sequence and the ribosome13,14. GTP is then hydrolysed so that SRP can be released from the SRP receptor and returned to the cytosol15. Here we show that the 54K subunit (M(r) 54,000) of SRP (SRP54) is a GTP-binding protein stabilized in a nucleotide-free state by signal sequences and that the SRP receptor both increases the affinity of SRP54 for GTP and activates its GTPase. We propose that nucleotide-mediated conformational changes in SRP54 regulate the release of signal sequences and the docking of ribosomes at the endoplasmic reticulum.