A two-way switch for inositol pyrophosphate signaling: Evolutionary history and biological significance of a unique, bifunctional kinase/phosphatase.

A two-way switch for inositol pyrophosphate signaling: Evolutionary history and biological significance of a unique, bifunctional kinase/phosphatase.
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DOI:
10.1016/j.jbior.2019.100674
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发表时间:
2020-01
影响因子:
--
通讯作者:
Shears, Stephen B.
Shears, Stephen B.
中科院分区:
其他
文献类型:
--
作者:
Randall, Thomas A.;Gu, Chunfang;Li, Xingyao;Wang, Huanchen;Shears, Stephen B.

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肌醇焦磷酸(PP-InsPs)是一个独特的亚群的细胞内信号与不同的功能,其中许多可以被视为反映了一个总体的作用,在代谢稳态。因此,相当多的注意力放在合成和代谢PP-InsPs的酶。这些酶家族之一-二磷酸肌醇五磷酸激酶(PPIP5Ks)-提供了一个非常罕见的例子,单独的激酶和磷酸酶活性存在于同一蛋白质中。在此,我们回顾了PPIP5Ks的结构/功能洞察的当前状态,两个后生动物PPIP5K基因的单独的专门活动,我们描述了一个系统发育分析,将PPIP5K的进化起源内的挖掘,最早的真核生物。PPIP5K生物学的这些不同方面被置于一个单一的、压倒一切的问题的背景下。为什么它们是双功能的:即,在一个蛋白质中,通过两个独立的"开关"开启或关闭PP-InsP信号传导的能力有什么特殊意义?
The inositol pyrophosphates (PP-InsPs) are a unique subgroup of intracellular signals with diverse functions, many of which can be viewed as reflecting an overarching role in metabolic homeostasis. Thus, considerable attention is paid to the enzymes that synthesize and metabolize the PP-InsPs. One of these enzyme families - the diphosphoinositol pentakisphosphate kinases (PPIP5Ks) - provides an extremely rare example of separate kinase and phosphatase activities being present within the same protein. Herein, we review the current state of structure/function insight into the PPIP5Ks, the separate specialized activities of the two metazoan PPIP5K genes, and we describe a phylogenetic analysis that places PPIP5K evolutionary origin within the Excavata, the very earliest of eukaryotes. These different aspects of PPIP5K biology are placed in the context of a single, overriding question. Why are they bifunctional: i.e., what is the particular significance of the ability to turn PP-InsP signaling on or off from two separate ‘switches’ in a single protein?
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