First steps of translocation elucidated Ribosomes synthesizing membrane or secretory proteins are targeted to the endoplasmic reticulum (ER) in eukaryotic cells by the signal recognition particle (SRP). Upon reaching the ER, the SRP interacts with its receptor to promote transfer of the signal sequence to the protein-conducting channel or translocon. Kobayashi et al. studied the ribosomal complex that forms on the ER, in which the SRP and its receptor interact to transfer the newly synthesized protein to the translocon. The observed organization of the assembly reveals the roles of multiple eukaryotic-specific protein components present in the SRP and its receptor in stabilizing the conformation that facilitates signal sequence handover. Science, this issue p. 323 Eukaryotic-specific signal recognition particle and receptor components stabilize the ribosomal endoplasmic reticulum–targeting complex. Signal recognition particle (SRP) targets proteins to the endoplasmic reticulum (ER). SRP recognizes the ribosome synthesizing a signal sequence and delivers it to the SRP receptor (SR) on the ER membrane followed by the transfer of the signal sequence to the translocon. Here, we present the cryo–electron microscopy structure of the mammalian translating ribosome in complex with SRP and SR in a conformation preceding signal sequence handover. The structure visualizes all eukaryotic-specific SRP and SR proteins and reveals their roles in stabilizing this conformation by forming a large protein assembly at the distal site of SRP RNA. We provide biochemical evidence that the guanosine triphosphate hydrolysis of SRP·SR is delayed at this stage, possibly to provide a time window for signal sequence handover to the translocon.

中文翻译：

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交接前哺乳动物核糖体 SRP•SRP 受体靶向复合物的结构

易位的第一步阐明了合成膜或分泌蛋白的核糖体通过信号识别粒子 (SRP) 靶向真核细胞中的内质网 (ER)。到达内质网后，SRP 与其受体相互作用以促进信号序列向蛋白质传导通道或转位子的转移。小林等人。研究了在 ER 上形成的核糖体复合物，其中 SRP 与其受体相互作用以将新合成的蛋白质转移到易位子。观察到的组装组织揭示了 SRP 及其受体中存在的多种真核特异性蛋白质组分在稳定促进信号序列切换的构象方面的作用。科学，这个问题 p。323 真核特异性信号识别颗粒和受体成分稳定核糖体内质网靶向复合物。信号识别颗粒 (SRP) 将蛋白质靶向内质网 (ER)。SRP 识别合成信号序列的核糖体，并将其传递给 ER 膜上的 SRP 受体 (SR)，然后将信号序列转移到易位子。在这里，我们展示了哺乳动物翻译核糖体与 SRP 和 SR 在信号序列切换之前的构象中复合的冷冻电子显微镜结构。该结构使所有真核特异性 SRP 和 SR 蛋白可视化，并通过在 SRP RNA 的远端部位形成大的蛋白质组装体来揭示它们在稳定这种构象中的作用。