The metaphorical swiss army knife: The multitude and diverse roles of HEAT domains in eukaryotic translation initiation.
The metaphorical swiss army knife: The multitude and diverse roles of HEAT domains in eukaryotic translation initiation.
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DOI：
10.1093/nar/gkac342
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发表时间：
2022-06-10
影响因子：
14.9
通讯作者：
Arthanari, Haribabu
中科院分区：
文献类型：
--
作者：
Friedrich, Daniel;Marintchev, Assen;Arthanari, Haribabu
由结构支架之间的特定相互作用形成的生物分子关联对于控制和调节细胞过程是至关重要的。其中一种以HEAT重复序列为特征的结构架构参与多种细胞过程，包括细胞内运输、信号传导和蛋白质合成。在这里，我们回顾了众多的和多功能性的HEAT域在mRNA翻译起始的调节。结构和细胞生物学方法以及一些生物物理学研究已经揭示了许多HEAT结构域介导的与许多蛋白质因子和RNA的相互作用协调翻译起始。我们描述了HEAT结构域的基本结构体系，并简要介绍了它们所指示的细胞过程的例子，包括核转运和RNA降解。然后，我们专注于翻译起始系统中具有HEAT结构域的蛋白质，特别是eIF 4G，DAP 5，eIF 5和eIF 2B的HEAT结构域。它们的显着的多功能相互作用，包括蛋白质-蛋白质和蛋白质-RNA识别的比较分析，揭示了这些热域内的柔性区域的功能重要性。在这里，我们概述了如何热域编排的翻译启动的基本方面，并强调该地区的开放机制的问题。
Biomolecular associations forged by specific interaction among structural scaffolds are fundamental to the control and regulation of cell processes. One such structural architecture, characterized by HEAT repeats, is involved in a multitude of cellular processes, including intracellular transport, signaling, and protein synthesis. Here, we review the multitude and versatility of HEAT domains in the regulation of mRNA translation initiation. Structural and cellular biology approaches, as well as several biophysical studies, have revealed that a number of HEAT domain-mediated interactions with a host of protein factors and RNAs coordinate translation initiation. We describe the basic structural architecture of HEAT domains and briefly introduce examples of the cellular processes they dictate, including nuclear transport by importin and RNA degradation. We then focus on proteins in the translation initiation system featuring HEAT domains, specifically the HEAT domains of eIF4G, DAP5, eIF5, and eIF2Bϵ. Comparative analysis of their remarkably versatile interactions, including protein–protein and protein–RNA recognition, reveal the functional importance of flexible regions within these HEAT domains. Here we outline how HEAT domains orchestrate fundamental aspects of translation initiation and highlight open mechanistic questions in the area.
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