Phosphorylation of a Human Microprotein Promotes Dissociation of Biomolecular Condensates,Journal of the American Chemical Society

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Phosphorylation of a Human Microprotein Promotes Dissociation of Biomolecular Condensates
Journal of the American Chemical Society ( IF 14.4 ) Pub Date : 2021-08-04 , DOI: 10.1021/jacs.1c05386
Zhenkun Na _{1,

2} , Yang Luo _{1,

2} , Danica S Cui ₁ , Alexandra Khitun _{1,

2} , Stephanie Smelyansky _{1,

2,

3} , J Patrick Loria _{1,

3} , Sarah A Slavoff _{1,

2,

3}

Affiliation

Proteogenomic identification of translated small open reading frames in humans has revealed thousands of microproteins, or polypeptides of fewer than 100 amino acids, that were previously invisible to geneticists. Hundreds of microproteins have been shown to be essential for cell growth and proliferation, and many regulate macromolecular complexes. However, the vast majority of microproteins remain functionally uncharacterized, and many lack secondary structure and exhibit limited evolutionary conservation. One such intrinsically disordered microprotein is NBDY, a 68-amino acid component of membraneless organelles known as P-bodies. In this work, we show that NBDY can undergo liquid–liquid phase separation, a biophysical process thought to underlie the formation of membraneless organelles, in the presence of RNA in vitro. Phosphorylation of NBDY drives liquid phase remixing in vitro and macroscopic P-body dissociation in cells undergoing growth factor signaling and cell division. These results suggest that NBDY phosphorylation enables regulation of P-body dynamics during cell proliferation and, more broadly, that intrinsically disordered microproteins may contribute to liquid–liquid phase separation and remixing behavior to affect cellular processes.

中文翻译：

人类微生物蛋白的磷酸化促进生物分子缩合物的解离

人类翻译的小开放阅读框的蛋白质组学鉴定揭示了数千种微生物蛋白，或少于 100 个氨基酸的多肽，这些以前对遗传学家来说是不可见的。数百种微生物蛋白已被证明对细胞生长和增殖至关重要，其中许多调节大分子复合物。然而，绝大多数微生物蛋白在功能上仍然没有特征，并且许多缺乏二级结构并且表现出有限的进化保守性。一种这样的本质上无序的微生物蛋白是 NBDY，它是一种被称为 P 体的无膜细胞器的 68 个氨基酸组成部分。在这项工作中，我们表明 NBDY 可以在体外存在 RNA 的情况下进行液-液相分离，这是一种被认为是无膜细胞器形成基础的生物物理过程. NBDY 的磷酸化驱动体外液相再混合和经历生长因子信号传导和细胞分裂的细胞中的宏观 P 体解离。这些结果表明，NBDY 磷酸化能够在细胞增殖过程中调节 P 体动力学，更广泛地说，本质上无序的微生物蛋白可能有助于液-液相分离和再混合行为以影响细胞过程。

更新日期：2021-08-19

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