DNA结合蛋白
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DNA结合蛋白(DNA-binding protein)是指能透过DNA结合结构域(DBD)与单链或双链DNA结合的一类蛋白质[1][2][3]。一般来说,能与特异DNA序列结合的DNA结合蛋白主要经由与B-DNA(生物体内DNA一般都是B-DNA形式)的大沟结合来识别DNA序列。因为B-DNA的大沟区域能容许更多蛋白质上的官能团靠近并与之进行相互作用[4][5]。
蛋白质与DNA的相互作用
[编辑]蛋白质与DNA的结合受到pH值、温度、离子强度、电场,以及大分子拥挤等多种条件的影响,具体分为特异性与非特异性两种。非特异性的结合指蛋白质与DNA的结合不依赖特定序列,而特异性的结合则只会发生在特定的DNA序列上[6][7]。在Cas9/CRSIPER系统出现前作为主流基因编辑工具的锌指蛋白以及TALENs都是依赖特异性的DNA蛋白间结合工作的[8]。
检测方法
[编辑]较早期的检测蛋白与DNA间相互作用的方法[9]包括凝胶迁移实验(EMSA)[10][11]、DNA-蛋白质相互作用ELISA实验(DPI-ELISA)[12]、DNA酶足迹法(DNase footprinting assay) [13]等等。而染色质免疫沉淀法(ChIP)则是目前较为通行的检测体内DNA与蛋白质相互作用的方法[14]。
非特异性DNA结合蛋白
[编辑]最常见的一种非特异性DNA结合蛋白是真核生物染色质中与DNA结合的组蛋白。组蛋白主要是通过所带的正电荷与带负电的DNA结合,所以组蛋白与DNA之间的结合不依赖DNA上的特定序列。这也符合组蛋白的生物学功能,因为组蛋白需要与各种不同的DNA片段结合形成染色质的基本组成单位核小体[15][16]。另外,真核生物染色质上能够使DNA链发生弯曲的高迁移率族(HMG)蛋白与DNA之间的结合也是非特异性的[17][18][19]。
特异性DNA结合蛋白
[编辑]很多特异性DNA结合蛋白属于转录因子。转录因子依赖其特有的DNA结合结构域与DNA上的特定序列结合。一般来说,转录因子在与DNA结合后,会招募酶对DNA或组蛋白进行修饰,进而调控基因的表达水平[20][21]。
参见
[编辑]参考文献
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