Hypothesis: structural heterogeneity of the unfolded proteins originating from the coupling of the local clusters and the long-range distance distribution
Hypothesis: structural heterogeneity of the unfolded proteins originating from the coupling of the local clusters and the long-range distance distribution
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DOI：
10.1007/s12551-018-0405-8
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发表时间：
2018-02
影响因子：
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通讯作者：
Satoshi Takahashi;Aya Yoshida;Hiroyuki Oikawa
中科院分区：
文献类型：
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作者：
Satoshi Takahashi;Aya Yoshida;Hiroyuki Oikawa
我们提出了一个假设，解释了关于未折叠蛋白质异质性的两个明显相互矛盾的观察结果。首先，单分子Förster共振能量转移(sm-FRET)光谱的线共聚焦方法显示，未折叠的蛋白质在FRET效率图中具有宽峰，这意味着持续时间长于毫秒的显著异质性。其次，荧光相关方法表明，未折叠的蛋白质在短于100纳秒的时间尺度内波动。为了阐明这一假设，我们首先总结了最近对未折叠蛋白质的结构和动力学的共识。接下来，我们讨论了传统的Sm-FRET光谱分析方法及其在分析未折叠蛋白质时的局限性，然后讨论了线共聚焦方法揭示异质性的优点。最后，我们认为疏水残基的局部聚集形成的结构异质性调节了标记生色团之间的远程距离的分布，导致FRET效率图中的峰变宽。生色团周围的疏水残基的聚集可能进一步有助于展宽。所提出的簇对于理解蛋白质折叠机制具有重要意义。
We propose a hypothesis that explains two apparently contradicting observations for the heterogeneity of the unfolded proteins. First, the line confocal method of the single-molecule Förster resonance energy transfer (sm-FRET) spectroscopy revealed that the unfolded proteins possess broad peaks in the FRET efficiency plot, implying the significant heterogeneity that lasts longer than milliseconds. Second, the fluorescence correlation method demonstrated that the unfolded proteins fluctuate in the time scale shorter than 100 ns. To formulate the hypothesis, we first summarize the recent consensus for the structure and dynamics of the unfolded proteins. We next discuss the conventional method of the sm-FRET spectroscopy and its limitations for the analysis of the unfolded proteins, followed by the advantages of the line confocal method that revealed the heterogeneity. Finally, we propose that the structural heterogeneity formed by the local clustering of hydrophobic residues modulates the distribution of the long-range distance between the labeled chromophores, resulting in the broadening of the peak in the FRET efficiency plot. A clustering of hydrophobic residues around the chromophore might further contribute to the broadening. The proposed clusters are important for the understanding of protein folding mechanism.