Following the signal sequence from ribosomal tunnel exit to signal recognition particle
Following the signal sequence from ribosomal tunnel exit to signal recognition particle
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DOI：
10.1038/nature05326
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发表时间：
2006-11-23
期刊：
影响因子：
64.8
通讯作者：
Beckmann, Roland
中科院分区：
文献类型：
--
作者：
Halic, Mario;Blau, Michael;Beckmann, Roland
膜蛋白和分泌蛋白可共翻译插入膜中或跨膜转运。这一过程依赖于信号识别颗粒（SRP）对核糖体上信号序列的识别，从而使核糖体 - 新生链复合物靶向膜上的蛋白质传导通道（2,3）。在此，我们展示了一组亚纳米分辨率的结构，揭示了核糖体通道出口处以及细菌和真核生物核糖体 - SRP复合物中的信号序列。通过拟合高分辨率分子模型，获得了原核和真核复合物中信号序列相互作用的分子细节。信号序列在核糖体通道出口处以暴露的位置呈现，准备容纳在重排的SRP54 M结构域的疏水凹槽中。在核糖体结合时，SRP54 NG结构域也会发生构象重排，为其随后与SRP受体的NG结构域的对接反应做好准备。这些发现为增进我们对共翻译蛋白质分选早期步骤的理解提供了结构基础。
Membrane and secretory proteins can be co-translationally inserted into or translocated across the membrane 1. This process is dependent on signal sequence recognition on the ribosome by the signal recognition particle (SRP), which results in targeting of the ribosome-nascent-chain complex to the protein-conducting channel at the membrane(2,3). Here we present an ensemble of structures at subnanometre resolution, revealing the signal sequence both at the ribosomal tunnel exit and in the bacterial and eukaryotic ribosome-SRP complexes. Molecular details of signal sequence interaction in both prokaryotic and eukaryotic complexes were obtained by fitting high-resolution molecular models. The signal sequence is presented at the ribosomal tunnel exit in an exposed position ready for accommodation in the hydrophobic groove of the rearranged SRP54 M domain. Upon ribosome binding, the SRP54 NG domain also undergoes a conformational rearrangement, priming it for the subsequent docking reaction with the NG domain of the SRP receptor. These findings provide the structural basis for improving our understanding of the early steps of co-translational protein sorting.