Biochemical propensity mapping for structural and functional anatomy of importin α IBB domain

Biochemical propensity mapping for structural and functional anatomy of importin α IBB domain
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输入蛋白 α IBB 结构域结构和功能解剖的生化倾向图

DOI:
10.1111/gtc.12917
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发表时间:
2022
期刊:
影响因子:
2.1
通讯作者:
Yasuhara Noriko
Yasuhara Noriko
中科院分区:
生物学4区
文献类型:
--
作者:
Jibiki Kazuya;Liu Mo‐yan;Lei Chao‐sen;Kodama Takashi S.;Kojima Chojiro;Fujiwara Toshimichi;Yasuhara Noriko

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Importin α被描述为核蛋白转运受体,使细胞质中合成的蛋白质转运到细胞核中。除了在核运输中的功能外,越来越多的研究已经研究了它的非核运输功能。在核转运和非核转运中,一个被称为伊布结构域(输入蛋白β结合结构域)的功能结构域在调节输入蛋白α行为中起关键作用,并且是多个结合伴侣的共同相互作用结构域。然而,目前尚不完全清楚伊布结构域如何与多个结合伙伴相互作用,从而导致输入蛋白α功能的切换。在这项研究中,我们通过将伊布结构域进化上保守的氨基酸的生化/物理化学倾向映射到与每个功能相关的结构上,区分了对importin α伊布结构域的每个功能重要的氨基酸的位置和倾向。我们发现了在物种和家族成员中伊布功能普遍保守的重要残基,除了先前已知的那些,以及被认为是家族成员之间复合物形成能力差异和功能转换的残基。
Importin α has been described as a nuclear protein transport receptor that enables proteins synthesized in the cytoplasm to translocate into the nucleus. Besides its function in nuclear transport, an increasing number of studies have examined its non‐nuclear transport functions. In both nuclear transport and non‐nuclear transport, a functional domain called the IBB domain (importin β binding domain) plays a key role in regulating importin α behavior, and is a common interacting domain for multiple binding partners. However, it is not yet fully understood how the IBB domain interacts with multiple binding partners, which leads to the switching of importin α function. In this study, we have distinguished the location and propensities of amino acids important for each function of the importin α IBB domain by mapping the biochemical/physicochemical propensities of evolutionarily conserved amino acids of the IBB domain onto the structure associated with each function. We found important residues that are universally conserved for IBB functions across species and family members, in addition to those previously known, as well as residues that are presumed to be responsible for the differences in complex‐forming ability among family members and for functional switching.
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