The conformation of a nascent polypeptide inside the ribosome tunnel affects protein targeting and protein folding.
The conformation of a nascent polypeptide inside the ribosome tunnel affects protein targeting and protein folding.
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DOI：
10.1111/j.1365-2958.2010.07325.x
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发表时间：
2010-10
影响因子：
3.6
通讯作者：
Bernstein HD
中科院分区：
文献类型：
--
作者：
Peterson JH;Woolhead CA;Bernstein HD
在本报告中，我们描述了通过分析与大肠杆菌 EspP 蛋白的信号肽相关的不寻常的 25 个残基 N 末端基序 (EspP1-25) 获得的对核糖体隧道功能的见解。之前的研究表明，EspP1-25 会抑制信号识别颗粒 (SRP) 的信号肽识别，现在我们发现 EspP1-25 与细胞质蛋白的融合会导致其聚集。我们获得了两条证据，表明这两种效应均可归因于核糖体隧道内 EspP1-25 的构象。首先，我们发现 EspP1-25 中的突变消除了其对蛋白质靶向和蛋白质折叠的影响，改变了新生短链与核糖体成分的交联。其次，我们发现 L22 中的一个突变会扭曲隧道，模仿了 EspP1-25 突变对蛋白质生物合成的影响。我们的结果提供了证据，证明核糖体通道内的多肽构象可以影响生理条件下的蛋白质折叠，并表明核糖体突变可能会增加大肠杆菌中产生的至少一些易于聚集的蛋白质的溶解度。
In this report we describe insights into the function of the ribosome tunnel that were obtained through an analysis of an unusual 25 residue N-terminal motif (EspP1-25) associated with the signal peptide of the E. coli EspP protein. It was previously shown that EspP1-25 inhibits signal peptide recognition by the signal recognition particle (SRP), and we now show that fusion of EspP1-25 to a cytoplasmic protein causes it to aggregate. We obtained two lines of evidence that both of these effects are attributable to the conformation of EspP1-25 inside the ribosome tunnel. First, we found that mutations in EspP1-25 that abolished its effects on protein targeting and protein folding altered the crosslinking of short nascent chains to ribosomal components. Second, we found that a mutation in L22 that distorts the tunnel mimicked the effects of the EspP1-25 mutations on protein biogenesis. Our results provide evidence that the conformation of a polypeptide inside the ribosome tunnel can influence protein folding under physiological conditions and suggest that ribosomal mutations might increase the solubility of at least some aggregation-prone proteins produced in E. coli.
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影响因子：
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