侧链相互作用在无序和PDZ域之间的结合反应中晚期和合作地形成
S Raza Haq1, Celestine N Chi, Anders Bach
1Department of Medical Biochemistry and Microbiology, Uppsala University, BMC Box 582, SE-75123 Uppsala, Sweden.
Journal of the American Chemical Society
|December 2, 2011
概括
内在无序的蛋白质形成弱的初始复合体. 原生相互作用在结合障碍之后发展,挑战了结合亲和力主要是由关联率驱动的理论.
科学领域:
- 生物化学 生物化学
- 分子生物学分子生物学
- 结构生物学 结构生物学
背景情况:
- 内在无序的蛋白质 (IDP) 对于细胞功能至关重要,它们调解重要的蛋白质-蛋白质和蛋白质-DNA相互作用.
- 尽管它们很重要,但控制IDP结合的分子机制仍然不太了解.
- 了解这些机制是解读细胞信号和调节的关键.
研究的目的:
- 使用型模型系统研究内在无序蛋白质的分子结合机制.
- 阐明本地侧链相互作用的作用,并在结合过程中遇到复杂物.
- 为了测试这种结合亲和力是由IDP的关联速率常数控制的假设.
主要方法:
- 利用短作为模型系统,代表内在无序的蛋白质.
- 使用速率和平衡结合常数应用线性自由能量关系.
- 研究了和有序标蛋白之间的相互作用,特别是PDZ域.
主要成果:
- 原生侧链相互作用主要是在结合的速度限制步骤之后形成的,这种相互作用是合作的.
- 失序的最初形成弱,非本地遭遇复合体.
- 结合亲和力 (Kd) 的变化与解离速率常数 (k_off) 相对应,而不是结合速率常数 (k_on).
结论:
- 本质上无序的蛋白质的结合机制涉及最初的非特异性相互作用,随后是障碍后的特定的合作性相互作用.
- 这项研究驳斥了这样一种观点,即内在流离失所者的结合亲和力通常是由关联率决定的.
- 分离率在确定-PDZ相互作用的整体亲和力方面发挥着更重要的作用.
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