Solvent-Driven Dynamical Crossover in the Phenylalanine Side-Chain from the Hydrophobic Core of Amyloid Fibrils Detected by 2H NMR Relaxation.
Solvent-Driven Dynamical Crossover in the Phenylalanine Side-Chain from the Hydrophobic Core of Amyloid Fibrils Detected by 2H NMR Relaxation.
复制标题
通过 2H NMR 弛豫检测到淀粉样原纤维疏水核心的苯丙氨酸侧链中溶剂驱动的动态交叉。
DOI：
10.1021/acs.jpcb.7b04726
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发表时间：
2017
期刊：
影响因子：
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通讯作者：
Falconer,IsaacB
中科院分区：
文献类型：
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作者：
Vugmeyster,Liliya;Ostrovsky,Dmitry;Hoatson,GinaL;Qiang,Wei;Falconer,IsaacB
芳香族残基是蛋白质疏水核心动态变化的重要标志。在这项工作中，我们研究了在300到140K的广泛温度范围内淀粉样纤维核心的F19侧链的动力学。我们利用固态2H核磁共振弛豫来证明不同运动区域之间存在溶剂驱动的动态交叉，也通常被称为动态转变。特别是，动力学在低温下由小角涨落主导，在高温下由芳环的π翻转所主导。与干燥状态相比，水合状态下纤维的交叉温度降低了43度以上，这表明与水的相互作用促进了π-Flip。此外，交叉温度对纤维的多态非常敏感，例如野生型蛋白质和D23N突变的原纤维的2倍和3倍对称形态。我们推测，这些差异可以归因于，至少部分归因于增强了与水的相互作用，在3重多晶型，已被证明有一个可水进入的空洞。结合以前对甲基动力学的研究，结果突出了纤维核心中存在多种动力学模式，最初被认为是相当刚性的。
Aromatic residues are important markers of dynamical changes in proteins’ hydrophobic cores. In this work we investigated the dynamics of the F19 side-chain in the core of amyloid fibrils across a wide temperature range of 300 to 140 K. We utilized solid-state2H NMR relaxation to demonstrate the presence of a solvent-driven dynamical crossover between different motional regimes, often also referred to as the dynamical transition. In particular, the dynamics are dominated by small-angle fluctuations at low temperatures and by π-flips of the aromatic ring at high temperatures. The crossover temperature is more than 43 degrees lower for the hydrated state of the fibrils compared to the dry state, indicating that interactions with water facilitate π-flips. Further, crossover temperatures are shown to be very sensitive to polymorphic states of the fibrils, such as the 2-fold and 3-fold symmetric morphologies of the wild-type protein as well as D23N mutant protofibrils. We speculate that these differences can be attributed, at least partially, to enhanced interactions with water in the 3-fold polymorph, which has been shown to have a water-accessible cavity. Combined with previous studies of methyl group dynamics, the results highlight the presence of multiple dynamics modes in the core of the fibrils, which was originally believed to be quite rigid.