在DNA聚合酶β的手指子域中的三元相互作用控制了聚合酶活性
Drew L Murphy1, Joachim Jaeger, Joann B Sweasy
1Department of Therapeutic Radiology, Yale University School of Medicine, New Haven, Connecticut 06520, USA.
Journal of the American Chemical Society
|April 2, 2011
概括
DNA聚合酶β (polβ),对于DNA修复至关重要,需要其C端区域的功能. 一个特定的突变揭示了聚合活性必不可少的关键相互作用.
科学领域:
- 生物化学 生物化学
- 分子生物学分子生物学
- 遗传学 是一个遗传学.
背景情况:
- DNA聚合酶β (polβ) 是基切除修复途径的核心.
- 以前的研究表明,聚β的C端区域对其功能至关重要.
研究的目的:
- 为了研究多β的C终端区域在DNA聚合中的作用.
- 为了阐明底层的分子机制聚β活动.
主要方法:
- 聚贝塔的C端区域的局部定向突变发生.
- 测量聚合酶活性的动力实验.
- 分子建模用于研究蛋白质相互作用和形状变化.
主要成果:
- C端区域对于野生类型的多β活性至关重要.
- 聚合化需要手指和手掌子域之间的相互作用.
- E316R突变体显示出聚合率显著降低,但保留了核酸结合.
- 破坏Arg182-Glu316相互作用会影响疏水性链区域的包装和形状变化.
结论:
- 聚β的C终端区域在DNA聚合中发挥着关键作用.
- 涉及Arg182,Glu316和Arg333的特定三元相互作用对多β功能至关重要.
- 在聚合过程中,核酸结合和核性攻击之间发生非共价步骤.
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