Importin alpha family NAAT/IBB domain: Functions of a pleiotropic long chameleon sequence
Importin alpha family NAAT/IBB domain: Functions of a pleiotropic long chameleon sequence
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导入α家族NAAT/IBB结构域：多效性长变色龙序列的功能
DOI：
10.1016/bs.apcsb.2022.11.005
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发表时间：
2023
期刊：
影响因子：
--
通讯作者：
Noriko Yasuhara
中科院分区：
文献类型：
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作者：
Kazuya Jibiki;Takashi S Kodama;Noriko Yasuhara
核运输是真核细胞生存所必需的，它通过核孔调节功能分子进出细胞核的运动。运输是通过货物和运输受体之间的蛋白质-蛋白质相互作用来促进的，这有助于表达和调节下游遗传信息。本章重点介绍Importinα家族多功能的分子基础，Importin家族是将蛋白质带入细胞核的代表性运输受体。Importinα通过与多个分子相互作用，在核转运过程中发挥多种功能，其结构域称为IBB结构域。这个结构域是一个很长的变色龙序列，它可以根据相互作用伙伴的不同而改变其构象和结合方式。通过考虑构成功能复合体界面的氨基酸的进化保守的生化/物理化学倾向及其结构特性，详细研究了通过IBB形成的多个复合体之间的切换机制和下游功能的调节。IBB的调节机制表明，我们看待蛋白质通过与其他分子相互作用来调节下游功能的分子机制的方式已经到了范式转变的时候。
Nuclear transport is essential for eukaryotic cell survival and regulates the movement of functional molecules in and out of the nucleus via the nuclear pore. Transport is facilitated by protein-protein interactions between cargo and transport receptors, which contribute to the expression and regulation of downstream genetic information. This chapter focuses on the molecular basis of the multifunctional nature of the importin α family, the representative transport receptors that bring proteins into the nucleus. Importin α performs multiple functions during the nuclear transport cycle through interactions with multiple molecules by a single domain called the IBB domain. This domain is a long chameleon sequence, which can change its conformation and binding mode depending on the interaction partners. By considering the evolutionarily conserved biochemical/physicochemical propensities of the amino acids constituting the functional complex interfaces, together with their structural properties, the mechanisms of switching between multiple complexes formed via IBB and the regulation of downstream functions are examined in detail. The mechanism of regulation by IBB indicates that the time has come for a paradigm shift in the way we view the molecular mechanisms by which proteins regulate downstream functions through their interactions with other molecules.