与 IP6K1 相互作用,支持肌醇焦磷酸 5-InsP7 对底物蛋白质进行焦磷酸化。

IF 3.8 3区 生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY
Aisha Hamid, Jayashree S Ladke, Akruti Shah, Shubhra Ganguli, Monisita Pal, Arpita Singh, Rashna Bhandari
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引用次数: 0

摘要

肌醇焦磷酸盐(PP-InsPs)是水溶性肌醇磷酸盐的一个亚家族,具有一个或多个二磷酸基团。PP-InsPs 可将其β-磷酸基转移到磷酸化的丝氨酸残基上,生成焦磷酸化丝氨酸。 这种独特的翻译后修饰发生在位于内在无序蛋白质序列中酸性绵延的丝氨酸残基上。丝氨酸焦磷酸化依赖于 Mg2+ 离子的存在,但不需要酶来催化。细胞调控 PP-InsP 介导的焦磷酸化的机制尚不清楚。我们用质谱法鉴定了 IP6K1(一种负责合成 PP-InsP 5-InsP7 的酶)的相互作用体。有趣的是,IP6K1 与几个已知会发生 5-InsP7 介导的焦磷酸化的蛋白质发生了相互作用,包括核仁蛋白 NOLC1、TCOF 和 UBF1 以及 AP3 适应蛋白复合物的 β 亚基 AP3B1。IP6K1 的相互作用组还包括 CK2,这是一种蛋白激酶,可在焦磷酸化之前使 Ser 残基磷酸化。我们观察到 IP6K1、AP3B1 和 CK2 的催化 α 亚基之间形成了一个蛋白复合物,并表明破坏 IP6K1 与 AP3B1 的结合会降低其体内焦磷酸化。我们提出,底物-CK2-IP6K 复合物的组装将使目标丝氨酸残基的预磷酸化和焦磷酸化得以协调进行,并提供了一种调节这种不依赖于酶的修饰的机制。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Interaction with IP6K1 supports pyrophosphorylation of substrate proteins by the inositol pyrophosphate 5-InsP7.

Inositol pyrophosphates (PP-InsPs) are a sub-family of water soluble inositol phosphates that possess one or more diphosphate groups. PP-InsPs can transfer their β-phosphate group to a phosphorylated Ser residue to generate pyrophosphorylated Ser. This unique post-translational modification occurs on Ser residues that lie in acidic stretches within an intrinsically disordered protein sequence. Serine pyrophosphorylation is dependent on the presence of Mg2+ ions, but does not require an enzyme for catalysis. The mechanisms by which cells regulate PP-InsP-mediated pyrophosphorylation are still unknown. We performed mass spectrometry to identify interactors of IP6K1, an enzyme responsible for the synthesis of the PP-InsP 5-InsP7. Interestingly, IP6K1 interacted with several proteins that are known to undergo 5-InsP7-mediated pyrophosphorylation, including the nucleolar proteins NOLC1, TCOF and UBF1, and AP3B1, the β subunit of the AP3 adaptor protein complex. The IP6K1 interactome also included CK2, a protein kinase that phosphorylates Ser residues prior to pyrophosphorylation. We observe the formation of a protein complex between IP6K1, AP3B1, and the catalytic α-subunit of CK2, and show that disrupting IP6K1 binding to AP3B1 lowers its in vivo pyrophosphorylation. We propose that assembly of a substrate-CK2-IP6K complex would allow for coordinated pre-phosphorylation and pyrophosphorylation of the target serine residue, and provide a mechanism to regulate this enzyme-independent modification.

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来源期刊
Bioscience Reports
Bioscience Reports 生物-细胞生物学
CiteScore
8.50
自引率
0.00%
发文量
380
审稿时长
6-12 weeks
期刊介绍: Bioscience Reports provides a home for sound scientific research in all areas of cell biology and molecular life sciences. Since 2012, Bioscience Reports has been fully Open Access and publishes all papers under the liberal CC BY licence, giving the life science community quality research to share and discuss.Content before 2012 is subscription-only, and is accessible via archive purchase. Articles are assessed on soundness, providing a home for valid findings and data. We welcome papers that span disciplines (e.g. chemistry, medicine), including papers describing: -new methodologies -tools and reagents to probe biological questions -mechanistic details -disease mechanisms -metabolic processes and their regulation -structure and function -bioenergetics
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