A cyclin-dependent kinase-mediated phosphorylation switch of disordered protein condensation.
A cyclin-dependent kinase-mediated phosphorylation switch of disordered protein condensation.
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DOI：
10.1038/s41467-023-42049-0
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发表时间：
2023-10-09
影响因子：
16.6
通讯作者：
Altelaar, Maarten
中科院分区：
文献类型：
--
作者：
Valverde, Juan Manuel;Dubra, Geronimo;Phillips, Michael;Haider, Austin;Elena-Real, Carlos;Fournet, Aurelie;Alghoul, Emile;Chahar, Dhanvantri;Andres-Sanchez, Nuria;Paloni, Matteo;Bernado, Pau;van Mierlo, Guido;Vermeulen, Michiel;van den Toorn, Henk;Heck, Albert J. R.;Constantinou, Angelos;Barducci, Alessandro;Ghosh, Kingshuk;Sibille, Nathalie;Knipscheer, Puck;Krasinska, Liliana;Fisher, Daniel;Altelaar, Maarten
细胞周期转变是由细胞周期蛋白依赖性蛋白激酶(CDKs)引起的蛋白质磷酸化状态的整体变化引起的。为了了解这种复杂性是如何产生有序而快速的细胞重组的，我们生成了一个高分辨率的地图，记录了单个非洲爪哇胚胎在不受干扰的早期细胞周期中不断变化的亚磷酸盐，通过系统生物学分析得出了涌现原理，并通过生物物理模型和生化实验对其进行了测试。我们发现大多数动态亚磷酸盐有两个关键特征：它们出现在定位于无膜细胞器的高度无序的蛋白质上，并且是CDK的靶标。此外，CDK介导的多位点磷酸化可以将这些蛋白质的同型相互作用在有利于和抑制生物分子缩合物形成的模式之间切换。这些结果为有丝分裂细胞重组的分子机制和动力学提供了洞察力。作者表明，脊椎动物细胞周期中蛋白质磷酸化的动态很大程度上归因于CDK介导的对参与生物分子凝聚体形成的内在无序蛋白质的调节。
Cell cycle transitions result from global changes in protein phosphorylation states triggered by cyclin-dependent kinases (CDKs). To understand how this complexity produces an ordered and rapid cellular reorganisation, we generated a high-resolution map of changing phosphosites throughout unperturbed early cell cycles in single Xenopus embryos, derived the emergent principles through systems biology analysis, and tested them by biophysical modelling and biochemical experiments. We found that most dynamic phosphosites share two key characteristics: they occur on highly disordered proteins that localise to membraneless organelles, and are CDK targets. Furthermore, CDK-mediated multisite phosphorylation can switch homotypic interactions of such proteins between favourable and inhibitory modes for biomolecular condensate formation. These results provide insight into the molecular mechanisms and kinetics of mitotic cellular reorganisation. The authors show that dynamics of protein phosphorylation in the vertebrate cell cycle is largely attributable to CDK-mediated regulation of intrinsically disordered proteins that are involved in biomolecular condensate formation.
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影响因子：
4.1
作者：
Curtis, M;Nikolopoulos, SN;Turner, CE
通讯作者：
Turner, CE
影响因子：
13.6
作者：
Chi, Yong;Carter, John H.;Clurman, Bruce E.
通讯作者：
Clurman, Bruce E.
影响因子：
12.3
作者：
Budnik B;Levy E;Harmange G;Slavov N
通讯作者：
Slavov N
DOI：
10.1098/rstb.2011.0074
发表时间：
2011-12-27
期刊：
Philosophical transactions of the Royal Society of London. Series B, Biological sciences
影响因子：
--
作者：
Hyman AA
通讯作者：
Hyman AA
DOI：
10.1073/pnas.0708966105
发表时间：
2008-02-05
影响因子：
11.1
作者：
Blethrow, Justin D.;Glavy, Joseph S.;Shokat, Kevan M.
通讯作者：
Shokat, Kevan M.