Diffracted X-ray tracking method for recording single-molecule protein motions
Diffracted X-ray tracking method for recording single-molecule protein motions
复制标题
用于记录单分子蛋白质运动的衍射X射线跟踪方法
DOI：
10.1016/j.bbagen.2019.05.004
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发表时间：
2019
期刊：
影响因子：
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通讯作者：
Shimizu Hirofumi
中科院分区：
文献类型：
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作者：
Koizumi Atsushi;Narita Shintaro;Nakanishi Hiroki;Ishikawa Masaki;Eguchi Satoshi;Kimura Hirotaka;Takasuga Shunsuke;Huang Mingguo;Inoue Takamitsu;Sasaki Junko;Yoshioka Toshiaki;Habuchi Tomonori;Sasaki Takehiko;Shimizu Hirofumi
研究背景蛋白质根据功能改变其构象。虽然已经积累了大量的蛋白质静态图片，但有关其功能动态的信息有限。衍射X射线跟踪（DXT）是一个很好的候选人，以获得缺失的data.Scope的审查一个金标记物作为探针连接到目标蛋白质和X射线衍射斑点的运动从晶体对应的运动的目标。虽然它具有高时间（亚毫秒）和空间（约0.1°）分辨率的优点，但它没有被广泛使用。这次审查的重点是从用户的角度来看其有效应用。我们还提出了一个例子与KcsA通道和最近的事态发展，以显示未来的可能性的方法。主要conclusionsDXT是一个强大的方法来调查分子内的结构变化。例如，在KcsA通道中，该方法揭示了从门区域传输到分子末端的构象变化波。该方法正在不断发展，用户可以根据样品的条件选择合适的测量系统。一般意义揭示蛋白质结构与功能的关系是一个重要的前沿领域。DXT方法最显著的特点是可以实现高的时间和空间分辨率，并且可以同时跟踪多个分子的运动。该特征对于筛选与靶蛋白相关的分子（例如，配体和药物）。
BackgroundProteins change their conformation depending on function. Although a vast number of static pictures of proteins have been accumulated, information regarding their dynamics in function is limited. Diffracted X-ray tracking (DXT) is a good candidate to obtain the missing data.Scope of reviewA gold nanocrystal was attached to the target protein as a probe and the motion of the X-ray diffraction spots from the crystal corresponded to the motion of the target. Although it has advantages of high temporal (sub-millisecond) and spatial (approximately 0.1°) resolutions, it is not extensively utilized. This review focused on its effective application from a user's perspective. We also present an example with the KcsA channel and the status of recent developments to show the future possibilities of the method.Major conclusionsDXT is a powerful method to investigate intramolecular structural changes. For instance, in the KcsA channel, the method revealed a wave of conformational changes transmitted from the gate region to the end of the molecule. The method is continuously being developed, and users can choose an appropriate measurement system depending on the condition of their sample.General significanceRevealing the protein structural changes with respect to function is an important frontier. The most distinctive feature of the DXT method is that both high temporal and spatial resolutions are achievable, and it is possible to track the motions of multiple molecules at the same time. This feature is an advantage for screening molecules associated with the target proteins (e.g., ligands and medicines).