Insertion and folding pathways of single membrane proteins guided by translocases and insertases
Insertion and folding pathways of single membrane proteins guided by translocases and insertases
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DOI：
10.1126/sciadv.aau6824
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发表时间：
2019-01-01
期刊：
影响因子：
13.6
通讯作者：
Mueller, Daniel J.
中科院分区：
文献类型：
--
作者：
Serdiuk, Tetiana;Steudle, Anja;Mueller, Daniel J.
原核生物和真核生物的生物发生需要α -螺旋蛋白插入细胞膜，它们使用普遍保守的细胞机制。在细菌的内膜中，YidC插入酶和SecYEG易位单独或协同作用促进了插入。插入酶和转座子如何将多肽折叠成膜中的天然蛋白在很大程度上是未知的。我们应用单分子力谱分析研究了在YidC和SecYEG的辅助下，单乳糖渗透酶（LacY）前体的插入和折叠过程。YidC和SecYEG都是通过插入单个结构片段来启动完全展开的多肽的折叠。然后YidC按随机顺序插入剩余的段，而SecYEG按顺序插入。每种类型的插入过程都将继续进行，直到LacY折叠完成。当YidC和SecYEG合作时，膜蛋白的折叠途径由转座酶主导。我们提出，YidC和SecYEG插入和折叠多肽的两种根本不同的途径都是膜蛋白生物发生的重要组成部分。
Biogenesis in prokaryotes and eukaryotes requires the insertion of alpha-helical proteins into cellular membranes for which they use universally conserved cellular machineries. In bacterial inner membranes, insertion is facilitated by YidC insertase and SecYEG translocon working individually or cooperatively. How insertase and translocon fold a polypeptide into the native protein in the membrane is largely unknown. We apply single-molecule force spectroscopy assays to investigate the insertion and folding process of single lactose permease (LacY) precursors assisted by YidC and SecYEG. Both YidC and SecYEG initiate folding of the completely unfolded polypeptide by inserting a single structural segment. YidC then inserts the remaining segments in random order, whereas SecYEG inserts them sequentially. Each type of insertion process proceeds until LacY folding is complete. When YidC and SecYEG cooperate, the folding pathway of the membrane protein is dominated by the translocase. We propose that both of the fundamentally different pathways along which YidC and SecYEG insert and fold a polypeptide are essential components of membrane protein biogenesis.