NAC functions as a modulator of SRP during the early steps of protein targeting to the endoplasmic reticulum.
NAC functions as a modulator of SRP during the early steps of protein targeting to the endoplasmic reticulum.
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DOI：
10.1091/mbc.e12-02-0112
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发表时间：
2012-08
影响因子：
3.3
通讯作者：
Rospert S
中科院分区：
文献类型：
--
作者：
Zhang Y;Berndt U;Gölz H;Tais A;Oellerer S;Wölfle T;Fitzke E;Rospert S
NAC作为SRP功能的调节器。它可以直接与信号序列结合。SRP最初取代了RNC中的NAC；然而，当信号序列出现时，形成了三聚体NAC·RNC·SRP复合体。当NAC·RNC·SRP复合体与内质网对接时，NAC仍然保持结合状态，使NAC能够保护暴露在细胞内的新生链域。新生多肽相关复合体(NAC)最初被发现与新生链除信号序列外的任何片段结合。通过这种方式，NAC被认为可以防止由于信号识别粒子(SRP)与无信号的核糖体新生链复合体(RNC)结合而导致的错误定位。在这里，我们重温NAC和SRP之间的相互作用。NAC不影响针对无信号RNC的SRP功能；但是，NAC确实影响针对内质网(ER)的RNC的SRP功能。首先，SRP在核糖体通道内对含有信号序列的RNC的早期募集是NAC依赖的。其次，NAC能够直接与新生信号序列紧密结合。第三，SRP最初取代了RNC中的NAC；然而，当信号序列进一步出现时，形成了三聚体NAC·RNC·SRP复合体。第四，当NAC与ER膜对接时，NAC仍然与RNC结合，使NAC不仅能够保护细胞学上暴露的新生链域，而且在共翻译易位期间也是如此。联合数据表明，NAC和SRP在内质网靶向RNC上存在功能相互作用，这是基于两个复合体同时与单个新生链段结合的能力。
NAC acts as a modulator of SRP function. It can bind to signal sequences directly. SRP initially displaces NAC from RNCs; however, when the signal sequence emerges, trimeric NAC·RNC·SRP complexes form. Upon docking NAC·RNC·SRP complexes to the ER, NAC remains bound, allowing NAC to shield cytosolically exposed nascent chain domains. Nascent polypeptide-associated complex (NAC) was initially found to bind to any segment of the nascent chain except signal sequences. In this way, NAC is believed to prevent mistargeting due to binding of signal recognition particle (SRP) to signalless ribosome nascent chain complexes (RNCs). Here we revisit the interplay between NAC and SRP. NAC does not affect SRP function with respect to signalless RNCs; however, NAC does affect SRP function with respect to RNCs targeted to the endoplasmic reticulum (ER). First, early recruitment of SRP to RNCs containing a signal sequence within the ribosomal tunnel is NAC dependent. Second, NAC is able to directly and tightly bind to nascent signal sequences. Third, SRP initially displaces NAC from RNCs; however, when the signal sequence emerges further, trimeric NAC·RNC·SRP complexes form. Fourth, upon docking to the ER membrane NAC remains bound to RNCs, allowing NAC to shield cytosolically exposed nascent chain domains not only before but also during cotranslational translocation. The combined data indicate a functional interplay between NAC and SRP on ER-targeted RNCs, which is based on the ability of the two complexes to bind simultaneously to distinct segments of a single nascent chain.