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Co-translational Folding Intermediate Dictates Membrane Targeting of the Signal Recognition Particle Receptor

机译：共转化折叠中间体决定了信号识别粒子受体的膜靶向

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Much of our knowledge on the function of proteins is deduced from their mature, folded states. However, it is unknown whether partially synthesized nascent protein segments can execute biological functions during translation and whether their premature folding states matter. A recent observation that a nascent chain performs a distinct function, co-translational targeting in vivo, has been made with the Escherichia coli signal recognition particle receptor FtsY, a major player in the conserved pathway of membrane protein biogenesis. FtsY functions as a membrane-associated entity, but very little is known about the mode of its targeting to the membrane. Here we investigated the underlying structural mechanism of the co-translational FtsY targeting to the membrane. Our results show that helices N-2_(4), which mediate membrane targeting, form a stable folding intermediate co-translationally that greatly differs from its fold in the mature FtsY. These results thus resolve a long-standing mystery of how the receptor targets the membrane even when deleted of its alleged membrane targeting sequence. The structurally distinct targeting determinant of FtsY exists only co-translationally. Our studies will facilitate further efforts to seek cellular factors required for proper targeting and association of FtsY with the membrane. Moreover, the results offer a hallmark example for how co-translational nascent intermediates may dictate biological functions. (C)2018 Elsevier Ltd. All rights reserved.
机译：我们对蛋白质功能的许多知识从他们的成熟，折叠状态推导出来。然而，尚不清楚是否可以在翻译期间能够执行生物学功能以及它们是否过早折叠状态的物质。最近一种观察到，新生链的表现为膜蛋白生物发生的保守途径中的主要参与者，已经用大肠杆菌信号识别粒子受体FTSY进行了不同的函数，在体内进行了共同转化靶向。 FTSY用作膜相关实体，但很少有关于其靶向膜的模式。在这里，我们调查了靶向膜的共转移FTSY的潜在结构机制。我们的结果表明，介导膜靶向的螺旋N-2_（4）形成稳定的折叠中间体，其具有极大地不同于其成熟FTSY中的折叠。因此，这些结果解决了即使当缺失其所谓的膜靶向序列时，受体如何将受体靶向膜的长期神秘。 FTSY的结构上不同的靶向靶点仅共同平移地存在。我们的研究将促进进一步努力寻求适当靶向和FTSY与膜结合所需的细胞因素。此外，结果提供了一个标志示例，了解共同转型的新生中间体可以决定生物学功能。 （c）2018年elestvier有限公司保留所有权利。

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