Folding transitions during assembly of the eukaryotic mRNA cap-binding complex.
Folding transitions during assembly of the eukaryotic mRNA cap-binding complex.
复制标题
真核 mRNA 帽结合复合物组装过程中的折叠转变。
DOI：
10.1016/j.jmb.2005.12.034
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发表时间：
2006
影响因子：
5.6
通讯作者：
McCarthy,JohnEG
中科院分区：
文献类型：
--
作者：
vonderHaar,Tobias;Oku,Yuko;Ptushkina,Marina;Moerke,Nathan;Wagner,Gerhard;Gross,JohnD;McCarthy,JohnEG
帽结合蛋白 eIF4E 是翻译起始因子链中的第一个，它将 40S 核糖体亚基募集到真核 mRNA 的 5' 端。在帽依赖性翻译过程中，该蛋白与 mRNA 的 5' 端 m7Gppp 帽以及接头蛋白 eIF4G 结合。然后后者与小核糖体亚基结合蛋白相互作用，从而促进 mRNA 募集过程。在这里，我们证明 apo-eIF4E 是一种含有大量非结构化区域的蛋白质，这些区域在识别帽子结构后被诱导折叠。 eIF4G 与 apo-eIF4E 的结合同样会诱导蛋白质折叠成与帽子结合的 eIF4E 相似但不相同的状态。同时，eIF4E 的每个结合配偶体的结合都会调节其与其他配偶体相互作用的动力学。我们提供了结构、动力学和诱变数据，使我们能够推断出 eIF4E 相互作用期间发生的一些详细折叠转变。
The cap-binding protein eIF4E is the first in a chain of translation initiation factors that recruit 40S ribosomal subunits to the 5′ end of eukaryotic mRNA. During cap-dependent translation, this protein binds to the 5′-terminal m7Gppp cap of the mRNA, as well as to the adaptor protein eIF4G. The latter then interacts with small ribosomal subunit-bound proteins, thereby promoting the mRNA recruitment process. Here, we show apo-eIF4E to be a protein that contains extensive unstructured regions, which are induced to fold upon recognition of the cap structure. Binding of eIF4G to apo-eIF4E likewise induces folding of the protein into a state that is similar to, but not identical with, that of cap-bound eIF4E. At the same time, binding of each of the binding partners of eIF4E modulates the kinetics with which it interacts with the other partner. We present structural, kinetic and mutagenesis data that allow us to deduce some of the detailed folding transitions that take place during the eIF4E interactions.