PDF(Pubmed)
Abstract：
Nascent polypeptide chains can induce translational stalling to regulate gene expression. This is exemplified by the E. coli secretion 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-length E. coli SecM 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.
摘要：
新生多肽链可以诱导翻译停滞以调节基因表达。例如大肠杆菌分泌监测（SecM）阻滞肽，其诱导翻译停滞以调节下游编码的SecA的表达，与SecYEG转位子协作以促进蛋白质插入或穿过细胞质膜的ATP酶。在这里，我们介绍了在全长大肠杆菌SecM阻滞肽翻译过程中停滞的核糖体的结构，分辨率为2.0。该结构揭示了SecM通过稳定A位点中的Pro-tRNA来阻止翻译，但是以防止与P位点中的SecM-肽基-tRNA形成肽键的方式。通过分子动力学模拟，我们还提供了有关SecM新生链上的拉力如何缓解SecM介导的翻译停滞的见解。总的来说，此处确定的SecM阻滞和缓解机制也可能适用于多种其他阻滞肽,这些阻滞肽调节在多种细菌谱系中鉴定的蛋白质定位机制的组分.
