An unusual signal peptide extension inhibits the binding of bacterial presecretory proteins to the signal recognition particle, trigger factor, and the SecYEG complex
An unusual signal peptide extension inhibits the binding of bacterial presecretory proteins to the signal recognition particle, trigger factor, and the SecYEG complex
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DOI：
10.1074/jbc.m508681200
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发表时间：
2006-04-07
影响因子：
4.8
通讯作者：
Bernstein, HD
中科院分区：
文献类型：
--
作者：
Peterson, JH;Szabady, RL;Bernstein, HD
大量证据表明，大肠杆菌信号识别颗粒（SRP）选择性地将含有高度疏水信号肽的蛋白质靶向SecYEG复合体共翻译。分泌前蛋白仅含有适度疏水的信号肽，通常与触发因子（TF）相互作用，并在翻译后靶向。在这里，我们描述了一个显著的例外，这一规则已经出现了一个不寻常的55个氨基酸信号肽与大肠杆菌自转运体EspP相关的分析。EspP信号肽由一个类似于经典信号肽的c端结构域和一个在其他自转运蛋白信号肽中保守的n端延伸组成。虽然先前的研究表明含有EspP信号肽c端结构域的蛋白被SRP共翻译靶向，但我们发现含有全长信号肽的蛋白在翻译后通过一种新的不依赖tf的机制被靶向。然而，在n端延伸中一个不变的天冬酰胺残基的突变恢复了共翻译靶向。值得注意的是，含有极疏水的EspP信号肽衍生物的蛋白质在翻译后也被靶向。这些结果和其他结果表明，n端延伸改变了信号肽对SRP和TF的可及性，并通过降低信号肽与SecYEG复合物之间相互作用的效率来促进翻译后输出。基于数据，我们提出n端延伸介导与未知细胞质因子的相互作用，或在蛋白质易位发生之前诱导异常信号肽构象的形成。
Considerable evidence indicates that the Escherichia coli signal recognition particle (SRP) selectively targets proteins that contain highly hydrophobic signal peptides to the SecYEG complex cotranslationally. Presecretory proteins that contain only moderately hydrophobic signal peptides typically interact with trigger factor (TF) and are targeted post-translationally. Here we describe a striking exception to this rule that has emerged from the analysis of an unusual 55-amino acid signal peptide associated with the E. coli autotransporter EspP. The EspP signal peptide consists of a C-terminal domain that resembles a classical signal peptide plus an N-terminal extension that is conserved in other autotransporter signal peptides. Although a previous study showed that proteins containing the C-terminal domain of the EspP signal peptide are targeted cotranslationally by SRP, we found that proteins containing the full-length signal peptide were targeted post-translationally via a novel TF-independent mechanism. Mutation of an invariant asparagine residue in the N-terminal extension, however, restored cotranslational targeting. Remarkably, proteins containing extremely hydrophobic derivatives of the EspP signal peptide were also targeted post-translationally. These and other results suggest that the N-terminal extension alters the accessibility of the signal peptide to SRP and TF and promotes post-translational export by reducing the efficiency of the interaction between the signal peptide and the SecYEG complex. Based on data, we propose that the N-terminal extension mediates an interaction with an unidentified cytoplasmic factor or induces the formation of an unusual signal peptide conformation prior to the onset of protein translocation.