Nanoscopic Dynamics Dictate the Phase Separation Behavior of Intrinsically Disordered Proteins.
Nanoscopic Dynamics Dictate the Phase Separation Behavior of Intrinsically Disordered Proteins.
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纳米动力学决定了本质无序蛋白质的相分离行为。
DOI：
10.1021/acs.biomac.0c01768
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发表时间：
2021
影响因子：
6.2
通讯作者：
D. Hinderberger
中科院分区：
文献类型：
--
作者：
Katharina Laaß;Felipe Garcia Quiroz;Johannes Hunold;S. Roberts;A. Chilkoti;D. Hinderberger
自然界中的许多内在无序蛋白质（IDP）可以经历液-液相分离以组装具有不同液体性质和稳定性/动力学的无膜细胞器。虽然溶解度变化的基础上这些属性，很少有人知道在相分离的IDP的水合动力学。在这里，通过研究类似的组合物，但不同的液体样的动力学和分离后的稳定性，即热滞后，IDP聚合物，我们探测在纳米级的水化/脱水动力学的IDP，因为它们可逆地在相分离状态之间切换。使用连续波电子顺磁共振（CW EPR）光谱，我们观察到不同的骨干和氨基酸侧链水合动力学在这些IDP。这种纳米级的观点表明，侧链再水化在主链骨架周围产生了一个动态的水盾，有效地和反直觉地防止水渗透并控制IDP溶解度。我们发现，这种表面的水壳的强度是一个序列特征的IDPs编码的稳定性，其相分离的组件。我们的研究结果揭示并提供了一个初步的了解如何纳米级水IDP相互作用的复杂性决定其丰富的相分离行为。
Many intrinsically disordered proteins (IDPs) in nature may undergo liquid-liquid phase separation to assemble membraneless organelles with varied liquid-like properties and stability/dynamics. While solubility changes underlie these properties, little is known about hydration dynamics in phase-separating IDPs. Here, by studying IDP polymers of similar composition but distinct liquid-like dynamics and stability upon separation, namely, thermal hysteresis, we probe at a nanoscopic level hydration/dehydration dynamics in IDPs as they reversibly switch between phase separation states. Using continuous-wave electron paramagnetic resonance (CW EPR) spectroscopy, we observe distinct backbone and amino acid side-chain hydration dynamics in these IDPs. This nanoscopic view reveals that side-chain rehydration creates a dynamic water shield around the main-chain backbone that effectively and counterintuitively prevents water penetration and governs IDP solubility. We find that the strength of this superficial water shell is a sequence feature of IDPs that encodes for the stability of their phase-separated assemblies. Our findings expose and offer an initial understanding of how the complexity of nanoscopic water-IDP interactions dictate their rich phase separation behavior.