通过 Fic 蛋白质的分子内或分子间活性部位阻塞来控制腺化
Philipp Engel1, Arnaud Goepfert, Frédéric V Stanger
1Focal Area Infection Biology, Biozentrum, University of Basel, CH-4056 Basel, Switzerland.
Nature
|January 24, 2012
概括
虚构蛋白通过催化腺化来调节细胞信号传递. 一个保留的抑制螺旋 (α(inh)) 阻断了ATP结合部位,控制了所有生命领域的这一活动.
科学领域:
- 生物化学 生物化学
- 分子生物学分子生物学
- 细胞生物学 细胞生物学
背景情况:
- 由FIC域定义的fic蛋白质催化蛋白质腺化 (AMPylation).
- 细菌Fic蛋白可以通过腺化哺乳动物GTPases引起细胞死亡.
- 在生活的各个领域中,对Fic蛋白腺化活性的调节了解甚少.
研究的目的:
- 阐明调节FIC域介导基化的保守机制.
- 研究抑制性α-螺旋 (α(inh)) 在控制Fic蛋白活性中的作用.
- 为了确定这个调节机制的进化保存.
主要方法:
- 对Fic蛋白的结构和功能分析,包括来自Bartonella schoenbuchensis的VbhT和VbhA.
- 生物化学测试以评估腺化活性.
- 标注Fic蛋白质的结构同质模型.
主要成果:
- 具有 (S/T) XXXE (G/N) 动图的保留抑制性α-螺旋 (α(inh)) 阻了ATP结合部位,调节了腺化.
- 在α(inh) 动图中不变的谷氨酸与ATP竞争.
- 观察到VbhA抗毒素的分子间抑制和α(inh) 延伸的分子内抑制.
- 抑制动机中的突变显著增加了腺化活性.
- 同性学建模表明,这种抑制机制在所有生命领域和病毒中约90%的FIC域中保持着.
结论:
- FIC域腺化通过ATP结合部位阻塞通过保留的抑制性α-螺旋被普遍控制.
- 这种调节机制是古老的和广泛的,在生命和病毒的所有领域都能找到.
- 未来的研究应该专注于细胞因子如何调节这种抑制.
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