Regulation of the interactions between human eIF5 and eIF1A by the CK2 kinase.
Regulation of the interactions between human eIF5 and eIF1A by the CK2 kinase.
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DOI：
10.1016/j.crstbi.2022.09.003
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发表时间：
2022
影响因子：
2.8
通讯作者：
Marintchev, Assen
中科院分区：
文献类型：
--
作者：
Gamble, Nathan;Paul, Eleanor Elise;Anand, Bibin;Marintchev, Assen
真核生物的翻译起始依赖于一个复杂的相互作用网络，在整个过程中不断重组。随着越来越多的关于核糖体起始前复合物（PIC）在翻译起始的不同阶段的结构信息的获得，关于哪些相互作用发生在何时，它们的作用和调控的新问题出现了。真核翻译因子（eIF） 5是GTPase eIF2的gtase激活蛋白（GAP），它将启动物Met-tRNAi带到PIC。eIF5还通过与其他蛋白（包括eIFs 1、1A和3c）的相互作用，在PIC组装和重塑中发挥核心作用。酪蛋白激酶2 （CK2）的磷酸化显著增加了eIF5对eIF2的亲和力。据报道，eIF5和eIF1A之间的相互作用是由eIF5 c端结构域（CTD）和eIF1A n端尾部介导的。在这里，我们报道了eIF5-CTD与eIF1A的寡核苷酸/寡糖结合折叠（OB）结构域之间的一个新的接触界面，这有助于两种蛋白之间的整体亲和力。我们还发现eIF5和eIF1A分子内的动态相互作用可以调节这种相互作用。CK2磷酸化eIF5增加其对eIF1A的亲和力，为CK2刺激蛋白合成和细胞增殖的机制提供了新的见解。eIF5-CTD与eIF1A的n端尾部和OB结构域相互作用。OB域联系人稳定了整个交互。eIF1A c端尾部和eIF5 DWEAR基序干扰OB结构域结合。CK2磷酸化eIF5增加其对eIF1A的亲和力。
Translation initiation in eukaryotes relies on a complex network of interactions that are continuously reorganized throughout the process. As more information becomes available about the structure of the ribosomal preinitiation complex (PIC) at various points in translation initiation, new questions arise about which interactions occur when, their roles, and regulation. The eukaryotic translation factor (eIF) 5 is the GTPase-activating protein (GAP) for the GTPase eIF2, which brings the initiator Met-tRNAi to the PIC. eIF5 also plays a central role in PIC assembly and remodeling through interactions with other proteins, including eIFs 1, 1A, and 3c. Phosphorylation by casein kinase 2 (CK2) significantly increases the eIF5 affinity for eIF2. The interaction between eIF5 and eIF1A was reported to be mediated by the eIF5 C-terminal domain (CTD) and the eIF1A N-terminal tail. Here, we report a new contact interface, between eIF5-CTD and the oligonucleotide/oligosaccharide-binding fold (OB) domain of eIF1A, which contributes to the overall affinity between the two proteins. We also show that the interaction is modulated by dynamic intramolecular interactions within both eIF5 and eIF1A. CK2 phosphorylation of eIF5 increases its affinity for eIF1A, offering new insights into the mechanisms by which CK2 stimulates protein synthesis and cell proliferation. eIF5-CTD interacts with both the N-terminal tail and the OB domain of eIF1A. The OB domain contacts stabilize the overall interaction. The eIF1A C-terminal tail and the eIF5 DWEAR motif interfere with OB domain binding. CK2 phosphorylation of eIF5 increases its affinity for eIF1A.