Early Scanning of Nascent Polypeptides inside the Ribosomal Tunnel by NAC
Early Scanning of Nascent Polypeptides inside the Ribosomal Tunnel by NAC
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DOI：
10.1016/j.molcel.2019.06.030
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发表时间：
2019-09-05
期刊：
影响因子：
16
通讯作者：
Deuerling, Elke
中科院分区：
文献类型：
--
作者：
Gamerdinger, Martin;Kobayashi, Kan;Deuerling, Elke
新合成蛋白质的共翻译加工是蛋白质正确成熟的基础。蛋白质生物合成因子被认为在它们离开核糖体隧道之前结合新生多肽。在这里，我们确定了一个新生的链识别机制的核糖体隧道深处的一个重要的真核细胞胞质伴侣。新生的多肽相关复合物（NAC）将其β亚基（N-beta NAC）的N-末端尾插入核糖体隧道中，以在合成后直接感测靠近肽基转移酶中心的底物。N-β NAC将生长的多肽护送到胞质溶胶并重新定位到核糖体表面上的替代结合位点。利用C.作为体内模型，我们证明NAC的隧道探测活性对于器官的存活是必不可少的，并且通过控制核糖体-Sec 61转位子相互作用来调节内质网（ER）蛋白转运是至关重要的。因此，真核蛋白质成熟依赖于核糖体隧道内新生链的早期取样。
Cotranslational processing of newly synthesized proteins is fundamental for correct protein maturation. Protein biogenesis factors are thought to bind nascent polypeptides not before they exit the ribosomal tunnel. Here, we identify a nascent chain recognition mechanism deep inside the ribosomal tunnel by an essential eukaryotic cytosolic chaperone. The nascent polypeptide-associated complex (NAC) inserts the N-terminal tail of its beta subunit (N-beta NAC) into the ribosomal tunnel to sense substrates directly upon synthesis close to the peptidyl-transferase center. N-beta NAC escorts the growing polypeptide to the cytosol and relocates to an alternate binding site on the ribosomal surface. Using C. elegans as an in vivo model, we demonstrate that the tunnel-probing activity of NAC is essential for organ ismal viability and critical to regulate endoplasmic reticulum (ER) protein transport by controlling ribosome-Sec61 translocon interactions. Thus, eukaryotic protein maturation relies on the early sampling of nascent chains inside the ribosomal tunnel.