Signal sequences activate the catalytic switch of SRP RNA.

Signal sequences activate the catalytic switch of SRP RNA.
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DOI:
10.1126/science.1165971
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发表时间:
2009-01-02
期刊:
Science (New York, N.Y.)
影响因子:
--
通讯作者:
Walter P
Walter P
中科院分区:
其他
文献类型:
--
作者:
Bradshaw N;Neher SB;Booth DS;Walter P

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信号识别颗粒(SRP)从核糖体中识别带有信号序列的多肽链,然后与其膜相关受体(SR)结合,从而将核糖体-新生链状复合体传递到真核细胞的内质网和原核细胞的质膜。SRP RNA催化SRP和SR的相互作用,从而刺激它们的鸟苷三磷酸酶(GTPase)活性,导致复合体的解离。我们发现,虽然SRP RNA的催化活性似乎是结构性的,但只有当SRP与信号序列结合时,SRP RNA才能加速复合体的形成。这一关键的控制步骤被掩盖了,因为反应缓冲液中通常包含的一种洗涤剂充当信号肽模拟物。因此,SRP RNA是一个分子开关,使SRP-SR GTP酶引擎对信号肽招募做出反应,将GTP水解与生产蛋白质靶向结合起来。
The signal recognition particle (SRP) recognizes polypeptide chains bearing a signal sequence as they emerge from the ribosome, and then binds its membrane-associated receptor (SR), thereby delivering the ribosome–nascent chain complex to the endoplasmic reticulum in eukaryotic cells and the plasma membrane in prokaryotic cells. SRP RNA catalytically accelerates the interaction of SRP and SR, which stimulates their guanosine triphosphatase (GTPase) activities, leading to dissociation of the complex. We found that although the catalytic activity of SRP RNA appeared to be constitutive, SRP RNA accelerated complex formation only when SRP was bound to a signal sequence. This crucial control step was obscured because a detergent commonly included in the reaction buffer acted as a signal peptide mimic. Thus, SRP RNA is a molecular switch that renders the SRP-SR GTPase engine responsive to signal peptide recruitment, coupling GTP hydrolysis to productive protein targeting.
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