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標題: FimX (EAL) 功能區域蛋白結合多型的c-di-GMP以及與第二型PilZ蛋白複合體晶體結構
Structural Polymorphism of c-di-GMP Bound to an EAL Domain of FimX and in Complex with a Type II PilZ domain Protein
作者: 郭威廷
Kuo, Wei-Ting
關鍵字: 環狀二鳥甘酸
出版社: 生物化學研究所
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摘要: c-di-GMP 是一個廣泛存在於細菌中的二級訊息傳遞分子。在結合各種不同的受器蛋白後,進而調節為數眾多的細菌生理活動。然而與c-di-GMP結合的受體蛋白是利用何種的機制來辨識結合至今仍尚未完全被瞭解。PilZ蛋白是一個對c-di-GMP具高親和力的接受體蛋白,到目前為止已有兩種類型的PilZ 蛋白被發現。而經由結合c-di-GMP後,第一型的PilZ 蛋白可參與調控鞭毛轉動的速率而影響細菌移動性。而第二型的PilZ 蛋白,細菌則利用它來調控纖毛的運動。根據先前研究中指出第四型纖毛的生合成,是由第二型的PilZ蛋白、c-di-GMP、以及一個具多個功能區域的蛋白FimX所參與的。然而目前尚未有相關的結構被解析。因此本研究以X-ray繞射技術解析出c-di-GMP與FimX(EAL)複合體結構以及第一個第二型的PilZ、FimX(EAL)及c-di-GMP之複合體結構。在解析出的結構中我們清楚的發現c-di-GMP結合在FimX蛋白複合體結構中的EAL功能區域,及位於PilZ蛋白與EAL功能區域的FimX蛋白複合體結構中的結合介面;然而在著兩個複合體結構中的c-di-GMP卻呈現不同的特殊單體構形。這些發現使我們推測c-di-GMP可能利用多種且具有彈性的構形,來辨識不同種的受器蛋白。此外利用恆溫滴定微卡計實驗與凝膠層析過濾法來檢查c-di-GMP對於形成複合體的重要性後發現。c-di-GMP對於形成XccimX(EAL)-c-di-GMP-XccPilZ的複合體結構是扮演著重要且必須的角色。這樣的結果使我們近一步瞭解第四型纖毛的生合成是如何受到c-di-GMP 控制,且c-di-GMP又是如何結合辨識多種的蛋白受器。
C-di-GMP is a novel secondary messenger molecule involved in regulating a plethora of important bacterial activities through binding to an unprecedented array of effectors. The mechanisms of c-di-GMP binding to so many distinct effectors remains poorly understood. Proteins with a canonical PilZ domain that binds c-di-GMP play crucial roles in regulating flagellum-based motility. In contrast, non-canonical type II PilZ domains that do not effectively bind c-di-GMP regulate twitching motility, which is dependent on type IV pilus (T4P).Recent data indicate that T4P biogenesis is initiated via interaction of a non-canonical type II PilZ protein with the GGDEF-EAL domain protein FimX and pilus motor protein PilB under high c-di-GMP concentration.However, the molecular details of such interactions remain to be elucidated. In this study, we report the first hetero-complex crystal structure of a type II PilZ protein and the EAL domain of FimX (FimX(EAL)) protein from Xcc(Xanthomnas campestris pv. campestris) in the presence of c-di-GMP. This work reveals two novel conformations for monomeric c-di-GMP in the XccFimX(EAL)-c-di-GMP and XccFimX(EAL)-c-di-GMP-XccPilZ complex structures and the unique interaction mode of type II PilZ domain with c-di-GMP. These findings indicate that c-di-GMP is flexible enough to adjust its conformations to match the corresponding recognition motifs of different cognate effectors. Altogether, the results represent a first step toward understanding of how T4P biogenesis is controlled by c-di-GMP at molecular level and also of the ability of c-di-GMP to bind to a wide variety of effectors.
其他識別: U0005-3107201215523500
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