Charge-controlled metastable liquid-liquid phase separation in protein solutions as a universal pathway towards crystallization

Charge-controlled metastable liquid-liquid phase separation in protein solutions as a universal pathway towards crystallization
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蛋白质溶液中电荷控制的亚稳态液-液相分离作为结晶的通用途径

DOI:
10.1039/c2sm07008a
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发表时间:
2012
期刊:
影响因子:
3.4
通讯作者:
F. Schreiber
F. Schreiber
中科院分区:
化学2区
文献类型:
--
作者:
F. Zhang;R. Roth;M. Wolf;F. Roosen-Runge;M. W. A. Skoda;R. M. J. Jacobs;R. Roth;M. Sztucki;F. Schreiber

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我们证明,室温下多价金属离子可以诱导蛋白质水溶液中的亚稳态液-液相分离(LLPS)。我们确定了两个共存相中盐和蛋白质的分配。小角度X射线散射获得的结构因子为短程吸引提供了直接证据,从而导致了LLPS的亚稳定性。具有三个控制参数(温度、蛋白质和盐浓度)的扩展相图提供了与第二维里系数标准一致的结论性物理图片。所提出的相行为等温控制机制为理解自然界中受控相行为开辟了新的视角。此外,我们讨论了该框架在预测和优化蛋白质结晶条件中的应用。
We demonstrate that a metastable liquid–liquid phase separation (LLPS) in protein aqueous solutions can be induced by multivalent metal ions at room temperature. We determine the salt and protein partitioning in the two coexisting phases. The structure factor obtained by small angle X-ray scattering provides direct evidence for a short-ranged attraction, which leads to the metastability of the LLPS. An extended phase diagram with three control parameters (temperature, protein and salt concentration) provides a conclusive physical picture consistent with a criterion for the second virial coefficient. The presented isothermal control mechanism of the phase behavior opens new perspectives for the understanding of controlled phase behavior in nature. Furthermore, we discuss the application of this framework in predicting and optimizing conditions for protein crystallization.
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