Liquid-Liquid Phase Separation of the Intrinsically Disordered Domain of the Fused in Sarcoma Protein Results in Substantial Slowing of Hydration Dynamics.

Liquid-Liquid Phase Separation of the Intrinsically Disordered Domain of the Fused in Sarcoma Protein Results in Substantial Slowing of Hydration Dynamics.
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肉瘤中融合蛋白质的内在无序结构域的液-液相分离导致水合动力学的显著减慢。

DOI:
10.1021/acs.jpclett.3c02790
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发表时间:
2023-12-14
影响因子:
5.7
通讯作者:
Hunger, Johannes
Hunger, Johannes
中科院分区:
化学2区
文献类型:
--
作者:
Krevert, Carola S.;Chavez, Daniel;Chatterjee, Sayantan;Stelzl, Lukas S.;Puetz, Sabine;Roeters, Steven J.;Rudzinski, Joseph F.;Fawzi, Nicolas L.;Girard, Martin;Parekh, Sapun H.;Hunger, Johannes

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液体凝析油的形成通过不同组分的局部化或通过改变流体动力运输在生物学中发挥着关键作用,但凝析油中对溶剂化至关重要的氢键环境仍然难以捉摸。我们探索了由融合在肉瘤蛋白的低复杂性结构域形成的缩合物中的氢键动力学。用蛋白质酰胺I振动的二维红外光谱研究凝聚蛋白的氢键动力学,我们发现酰胺I振动的频率-频率关联在皮秒的时间尺度上衰减。有趣的是,凝结物中的蛋白质的这些动力学明显慢于均相蛋白质溶液中的蛋白质,这表明不同的水化动力学。全原子分子动力学模拟证实,在凝聚体中,水与蛋白质之间的氢键寿命比在溶液中的蛋白质长。氢键动力学的改变可能有助于这种凝析油中独特的溶剂化和反应动力学。
Formation of liquid condensates plays a critical role in biology via localization of different components or via altered hydrodynamic transport, yet the hydrogen-bonding environment within condensates, pivotal for solvation, has remained elusive. We explore the hydrogen-bond dynamics within condensates formed by the low-complexity domain of the fused in sarcoma protein. Probing the hydrogen-bond dynamics sensed by condensate proteins using two-dimensional infrared spectroscopy of the protein amide I vibrations, we find that frequency–frequency correlations of the amide I vibration decay on a picosecond time scale. Interestingly, these dynamics are markedly slower for proteins in the condensate than in a homogeneous protein solution, indicative of different hydration dynamics. All-atom molecular dynamics simulations confirm that lifetimes of hydrogen-bonds between water and the protein are longer in the condensates than in the protein in solution. Altered hydrogen-bonding dynamics may contribute to unique solvation and reaction dynamics in such condensates.
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