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细胞色素促使其核伴侣SET/TAF-Iβ和NPM1募集到生物分子凝聚物中。

Cytochrome prompts the recruitment of its nuclear partners SET/TAF-Iβ and NPM1 into biomolecular condensates.

作者信息

Casado-Combreras Miguel Á, Velázquez-Campoy Adrián, Martinho Marlène, Belle Valérie, De la Rosa Miguel A, Díaz-Moreno Irene

机构信息

Institute for Chemical Research (IIQ), Scientific Research Center "Isla de la Cartuja" (cicCartuja), University of Seville - CSIC, Seville, Spain.

Institute for Biocomputation and Physic of Complex Systems (BIFI), Joint Unit GBsC-CSIC-BIFI, University of Zaragoza, Zaragoza, Spain.

出版信息

iScience. 2024 Jul 2;27(8):110435. doi: 10.1016/j.isci.2024.110435. eCollection 2024 Aug 16.

DOI:10.1016/j.isci.2024.110435
PMID:39108706
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11301353/
Abstract

Compartmentalization of proteins by liquid-liquid phase separation (LLPS) is used by cells to control biochemical reactions spatially and temporally. Among them, the recruitment of proteins to DNA foci and nucleolar trafficking occur by biomolecular condensation. Within this frame, the oncoprotein SET/TAF-Iβ plays a key role in both chromatin remodeling and DNA damage response, as does nucleophosmin (NPM1) which indeed participates in nucleolar ribosome synthesis. Whereas phase separation by NPM1 is widely characterized, little is known about that undergone by SET/TAF-Iβ. Here, we show that SET/TAF-Iβ experiences phase separation together with respiratory cytochrome (C), which translocates to the nucleus upon DNA damage. Here we report the molecular mechanisms governing C-induced phase separation of SET/TAF-Iβ and NPM1, where two lysine-rich clusters of C are essential to recognize molecular surfaces on both partners in a specific and coordinated manner. C thus emerges as a small, globular protein with sequence-encoded heterotypic phase-separation properties.

摘要

细胞利用液-液相分离（LLPS）对蛋白质进行区室化，从而在空间和时间上控制生化反应。其中，蛋白质向DNA病灶的募集和核仁运输是通过生物分子凝聚发生的。在此框架内，癌蛋白SET/TAF-Iβ在染色质重塑和DNA损伤反应中均起关键作用，核磷蛋白（NPM1）也是如此，它确实参与核仁核糖体的合成。虽然NPM1的相分离已得到广泛表征，但关于SET/TAF-Iβ的相分离却知之甚少。在这里，我们表明SET/TAF-Iβ与呼吸细胞色素C一起经历相分离，细胞色素C在DNA损伤时会转运到细胞核。在此我们报告了控制细胞色素C诱导SET/TAF-Iβ和NPM1相分离的分子机制，其中细胞色素C的两个富含赖氨酸的结构域对于以特定且协调的方式识别两个伴侣分子表面至关重要。因此，细胞色素C是一种具有序列编码的异型相分离特性的小型球状蛋白。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/05d8/11301353/011839b02b54/gr6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/05d8/11301353/024e37c27791/fx1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/05d8/11301353/2de0f747c396/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/05d8/11301353/ee1391900b99/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/05d8/11301353/d7b8791bafaf/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/05d8/11301353/2d8d39a3dae9/gr4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/05d8/11301353/9e816b3ddf5e/gr5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/05d8/11301353/011839b02b54/gr6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/05d8/11301353/024e37c27791/fx1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/05d8/11301353/2de0f747c396/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/05d8/11301353/ee1391900b99/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/05d8/11301353/d7b8791bafaf/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/05d8/11301353/2d8d39a3dae9/gr4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/05d8/11301353/9e816b3ddf5e/gr5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/05d8/11301353/011839b02b54/gr6.jpg

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本文引用的文献

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Nat Commun. 2023 Sep 21;14(1):5892. doi: 10.1038/s41467-023-41586-y.
2
The Histone Chaperones SET/TAF-1β and NPM1 Exhibit Conserved Functionality in Nucleosome Remodeling and Histone Eviction in a Cytochrome c-Dependent Manner.组蛋白伴侣 SET/TAF-1β 和 NPM1 以细胞色素 c 依赖性方式在核小体重塑和组蛋白驱逐中表现出保守功能。
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Cytochrome c lysine acetylation regulates cellular respiration and cell death in ischemic skeletal muscle.
细胞色素 c 酪氨酸 48 位的磷酸化精细调节其在核内与组蛋白伴侣 SET/TAF-Iβ 的结合。
Protein Sci. 2024 Dec;33(12):e5213. doi: 10.1002/pro.5213.
细胞色素 c 赖氨酸乙酰化调节缺血性骨骼肌中的细胞呼吸和细胞死亡。
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Liquid-Liquid Phase Separation Modifies the Dynamic Properties of Intrinsically Disordered Proteins.液-液相分离改变了无序蛋白的动态特性。
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