Water molecular system dynamics associated with amyloidogenic nucleation as revealed by real time near infrared spectroscopy and aquaphotomics.
Water molecular system dynamics associated with amyloidogenic nucleation as revealed by real time near infrared spectroscopy and aquaphotomics.
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DOI：
10.1371/journal.pone.0101997
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Tsenkova R
中科院分区：
文献类型：
--
作者：
Chatani E;Tsuchisaka Y;Masuda Y;Tsenkova R
淀粉样蛋白原纤维的形成通过成核依赖性机制进行，其中成核阶段通常与导致限速步骤的高自由能相关。基于这种动力学特征，成核是控制淀粉样变性发病的最关键阶段之一，但关于蛋白质分子和周围环境在此阶段如何变化的细节知之甚少。在这里，我们应用近红外（NIR）光谱监测水的结构变化在真实的时间在成核依赖性纤维化的胰岛素。虽然在2050-2350 nm光谱区的多变量光谱分析表明交叉β形成，但在1300-1600 nm光谱区检测到水结构的特征转变，对应于水OH伸缩振动的第一泛音。此外，在蛋白质成核和聚集的过程中，沿着发现了与不同水分子构象相关的特定水光谱模式（aquagrams）。刚开始时，在本体水的氢键网络的解离和同时蛋白质和离子水合观察，随后水氢键网络的发展，大概迫使成核。这些特定的转换水的光谱模式，可进一步作为一种生物标志物，用于早期非侵入性诊断淀粉样变性之前的爆炸性扩增和沉积的淀粉样纤维。
The formation of amyloid fibrils proceeds via a nucleation-dependent mechanism in which nucleation phase is generally associated with a high free energy resulting in the rate-limiting step. On the basis of this kinetic feature, the nucleation is one of the most crucial phases controlling the pathogenesis of amyloidoses, but little is known about the details of how protein molecules and surrounding environment vary at this stage. Here, we applied near infrared (NIR) spectral monitoring of water structural changes in real time during the nucleation-dependent fibrillation of insulin. Whilst multivariate spectral analysis in the 2050–2350 nm spectral region indicated cross-β formation, characteristic transformations of water structure have been detected in the spectral region 1300–1600 nm corresponding to the first overtone of water OH stretching vibrations. Furthermore, specific water spectral patterns (aquagrams) related to different water molecular conformations have been found along the course of protein nucleation and aggregation. Right in the beginning, dissociation of hydrogen-bonded network in bulk water and coinstantaneous protein and ion hydration were observed, followed by water hydrogen-bonded networks development, presumably forcing the nucleation. These specific transformations of water spectral pattern could be used further as a biomarker for early non-invasive diagnosis of amyloidoses prior to explosive amplification and deposits of amyloid fibrils.
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影响因子：
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影响因子：
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Kinoshita, Kodzue;Miyazaki, Mari;Morita, Hiroyuki;Vassileva, Maria;Tang, Chunxiang;Li, Desheng;Ishikawa, Osamu;Kusunoki, Hiroshi;Tsenkova, Roumiana
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