Phosphorylation of a Human Microprotein Promotes Dissociation of Biomolecular Condensates.
Phosphorylation of a Human Microprotein Promotes Dissociation of Biomolecular Condensates.
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人类微蛋白的磷酸化促进了生物分子冷凝物的解离。
DOI：
10.1021/jacs.1c05386
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发表时间：
2021-08-18
影响因子：
15
通讯作者：
Slavoff SA
中科院分区：
文献类型：
--
作者：
Na Z;Luo Y;Cui DS;Khitun A;Smelyansky S;Loria JP;Slavoff SA
人类翻译的小开放阅读框的蛋白质基因组学鉴定已经揭示了数千个微蛋白，或少于100个氨基酸的多肽，这些蛋白质以前是遗传学家看不见的。数以百计的微蛋白已被证明是细胞生长和增殖所必需的，许多调节大分子复合物。然而，绝大多数微蛋白在功能上仍未被表征，许多微蛋白缺乏二级结构，并表现出有限的进化保守性。其中一种内在无序的微蛋白是NBDY，它是一种由68个氨基酸组成的无膜细胞器p体。在这项工作中，我们表明NBDY可以在体外RNA存在的情况下进行液-液相分离，这是一种生物物理过程，被认为是无膜细胞器形成的基础。NBDY的磷酸化驱动体外液相再混合和生长因子信号传导和细胞分裂过程中p体的宏观解离。这些结果表明，NBDY磷酸化可以调节细胞增殖过程中的p体动力学，更广泛地说，内在无序的微蛋白可能有助于液-液相分离和再混合行为，从而影响细胞过程。
Proteogenomic identification of translated small open reading frames in human 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.
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影响因子：
16.6
作者：
Cao X;Khitun A;Luo Y;Na Z;Phoodokmai T;Sappakhaw K;Olatunji E;Uttamapinant C;Slavoff SA
通讯作者：
Slavoff SA
影响因子：
7.3
作者：
Fan QW;Cheng C;Knight ZA;Haas-Kogan D;Stokoe D;James CD;McCormick F;Shokat KM;Weiss WA
通讯作者：
Weiss WA
影响因子：
5.4
作者：
Dull, T;Zufferey, R;Naldini, L
通讯作者：
Naldini, L
影响因子：
21.8
作者：
Aumiller, William M., Jr.;Keating, Christine D.
通讯作者：
Keating, Christine D.
影响因子：
3.7
作者：
Garmendia-Torres C;Skupin A;Michael SA;Ruusuvuori P;Kuwada NJ;Falconnet D;Cary GA;Hansen C;Wiggins PA;Dudley AM
通讯作者：
Dudley AM