The SecM arrest peptide traps a pre-peptide bond formation state of the ribosome
The SecM arrest peptide traps a pre-peptide bond formation state of the ribosome
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DOI：
10.1038/s41467-024-46762-2
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发表时间：
2024-03-19
影响因子：
16.6
通讯作者：
Wilson，Daniel N.
中科院分区：
文献类型：
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作者：
Gersteuer，Felix;Morici，Martino;Wilson，Daniel N.
新生多肽链可以诱导翻译停滞来调节基因表达。这是由E.大肠杆菌分泌监测（SecM）阻滞肽，其诱导翻译停滞以调节下游编码的SecA的表达，SecA是与SecYEG易位子合作以促进蛋白质插入或穿过细胞质膜的ATP酶。在这里，我们提出了一个核糖体的结构，在翻译过程中停滞的全长E。coliSecM捕获肽，分辨率为2.0 μ m。该结构揭示了SecM通过稳定A位点的Pro-tRNA来阻止翻译，但以防止与P位点的SecM-肽基-tRNA形成肽键的方式。通过采用分子动力学模拟，我们还提供了洞察力如何在SecM新生链上的拉力可以缓解SecM介导的翻译停滞。总的来说，这里确定的SecM逮捕和救济的机制也可能适用于各种其他逮捕肽，调节在广泛的细菌谱系中鉴定的蛋白质定位机制的组成部分。
Nascent polypeptide chains can induce translational stalling to regulate gene expression. This is exemplified by theE. colisecretion monitor (SecM) arrest peptide that induces translational stalling to regulate expression of the downstream encoded SecA, an ATPase that co-operates with the SecYEG translocon to facilitate insertion of proteins into or through the cytoplasmic membrane. Here we present the structure of a ribosome stalled during translation of the full-lengthE. coliSecM arrest peptide at 2.0 Å resolution. The structure reveals that SecM arrests translation by stabilizing the Pro-tRNA in the A-site, but in a manner that prevents peptide bond formation with the SecM-peptidyl-tRNA in the P-site. By employing molecular dynamic simulations, we also provide insight into how a pulling force on the SecM nascent chain can relieve the SecM-mediated translation arrest. Collectively, the mechanisms determined here for SecM arrest and relief are also likely to be applicable for a variety of other arrest peptides that regulate components of the protein localization machinery identified across a wide range of bacteria lineages.