Disorder is a critical component of lipoprotein sorting in Gram-negative bacteria
Disorder is a critical component of lipoprotein sorting in Gram-negative bacteria
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DOI：
10.1038/s41589-021-00845-z
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发表时间：
2021-07-29
影响因子：
14.8
通讯作者：
Csoma, Naemi
中科院分区：
文献类型：
--
作者：
El Rayes, Jessica;Szewczyk, Joanna;Csoma, Naemi
革兰氏阴性细菌在其细胞包膜中表达结构多样的脂蛋白。在这里，我们发现大约一半的脂蛋白被运往大肠杆菌外膜，在其 N 末端显示出本质上无序的连接子。本质上无序的区域在蛋白质中很常见，但确定它们在体内的重要性仍然具有挑战性。当我们试图解开脂蛋白成熟的过程时，我们发现 Lol 脂蛋白分选系统需要非结构化接头来实现最佳运输，从而接头删除将三种不相关的脂蛋白重新路由到内膜。着眼于应力传感器 RcsF，我们发现，只有当肽长度相似且无序时，用人工肽替换接头才能恢复正常的外膜靶向。总的来说，这项研究揭示了脂蛋白分选中内在紊乱所发挥的作用，为这些蛋白质的生物发生提供了机制上的见解，并表明进化可以选择支持蛋白质功能的内在紊乱。
Gram-negative bacteria express structurally diverse lipoproteins in their cell envelope. Here, we find that approximately half of lipoproteins destined to the Escherichia coli outer membrane display an intrinsically disordered linker at their N terminus. Intrinsically disordered regions are common in proteins, but establishing their importance in vivo has remained challenging. As we sought to unravel how lipoproteins mature, we discovered that unstructured linkers are required for optimal trafficking by the Lol lipoprotein sorting system, whereby linker deletion re-routes three unrelated lipoproteins to the inner membrane. Focusing on the stress sensor RcsF, we found that replacing the linker with an artificial peptide restored normal outer-membrane targeting only when the peptide was of similar length and disordered. Overall, this study reveals the role played by intrinsic disorder in lipoprotein sorting, providing mechanistic insight into the biogenesis of these proteins and suggesting that evolution can select for intrinsic disorder that supports protein function.