有些蛋白質區段在生理環境下無法形成穩定的立體結構，稱之為非穩定區段（disordered regions）。非穩定區段已被證實參與各種分子交互作用並在生物反應（例如轉錄調控與訊息傳遞）中扮演了重要的角色，其中最明顯的證據是許多蛋白質的非穩定區段在結合其他生物分子後會轉變成穩定區段。過去有許多研究蒐集結合前後的蛋白質結構對來分析這種構形轉變（conformational changes），然而，這些研究主要探討結合特定分子的構形轉變，往往僅依賴單一結構對來分析單一蛋白質，而忽略蛋白質在不同的環境下可能結合不同的分子並發生不同的構形轉變。
本論文提出一套新的蛋白質結構對蒐集方法，我們將結合的分子分為蛋白質、DNA與配體三個種類，並用多個蛋白質對來分析單一蛋白質，這樣的設計可以分析非穩定區段在結合不同種類分子下構形轉變的差異。實驗結果顯示相較於一般非穩定區段，發生構形轉變的部分更接近結合的分子，說明構形轉變在結合中的確扮演著重要的角色。另外不同種類的結合分子對非穩定區段的需求不同，結合DNA分子的蛋白質中有非穩定區段的比例最高，表示蛋白質需要更多非穩定區來結合DNA。
本研究總共蒐集了超過四萬組蛋白質結構對，包含超過三千多個蛋白質，相較於以往僅使用數百個蛋白質結構對的分析，提供了更全面且更精確的結果。這些結構對也可以拿來分析蛋白質結構在結合前後其他的變化，例如蛋白質二級結構、磷酸化等等。

Many protein segments, called disordered regions, do not form stable tertiary structures under physiological conditions. Such disordered regions have been shown participate in various molecule interactions and play important roles in biological processes such as transcription regulation and signal transduction, where the most obvious evidence is that some disordered regions become ordered after the interaction. Recently many studies collected structure pairs of proteins before and after binding to study such disorder-to-order conformational changes. However, these studies focused on conformational changes of binding specific molecules. Furthermore, they usually used only one structure pair to represent a protein but ignore that proteins may bind different molecules and have different conformational changes under different conditions.
This study proposed a novel scheme of collecting protein structure pairs before and after binding. We categorized the binding partners into proteins, DNAs and ligands and allowed multiple structure pairs representing the same protein. Thus, we can analyze the conformational changes of protein structures while binding molecules of different types. The experimental results show that the regions with conformational changes were closer to the binding partner in comparison with the other disordered regions. This reveals that conformational changes play an important role in molecule binding. In addition, binding different molecule types have different needs for disordered regions. In our results, for example, DNA-binding proteins had more disordered regions, indicating that proteins need more disordered regions to bind DNAs.
This study collected more than 40000 protein structure pairs, covering more than 3000 proteins. In comparison with previous studies analyzing only hundreds of structure pairs, this study provided more comprehensive and precise analyses. Furthermore, these structure pairs can be used to analyze other protein structural changes, such as secondary structure and phosphorylation, before and after binding.

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