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通过并列指蛋白诱导适应性结合
Anamika Patel1, Peng Yang2, Matthew Tinkham2
1Department of Biochemistry, Emory University School of Medicine, 1510 Clifton Road, Atlanta, GA 30322, USA.
Cell
|March 20, 2018
概括
指 (ZF) 蛋白调节基因. 这项研究揭示了ZFP568蛋白与DNA的相互作用,为哺乳动物的发展和进化提供了洞察力.
科学领域:
- 分子生物学
- 遗传学
- 进化生物学
背景情况:
- 双联指 (ZF) 蛋白代表了哺乳动物中DNA结合转录调节者的最大和最快进化的家族.
- 在小鼠中,ZFP568被确定为胎盘特异性胰岛素类生长因子2 (Igf2- P0) 转录的抑制剂.
研究的目的:
- 阐明ZFP568的DNA结合机制.
- 研究ZF-DNA相互作用的结构动态和进化适应性.
主要方法:
- 分析ZFP568与Igf2-P0上游的特定24元素的结合.
- 在ZF蛋白结合过程中检查DNA和蛋白质构成.
主要成果:
- ZFP568使用11-ZF阵列来结合Igf2-P0调节元件.
- 从传统的ZF-DNA识别中观察到的偏差,个别的ZF接触不同数量的 (2-4) 并识别相反的.
- 由于富含AT的序列而缩短的小沟相互作用突出显示了ZF阵列的适应性.
- 在黑猩猩和人类中Igf2和ZFP568的突变降低了结合亲和力,尽管哺乳动物的保护.
结论:
- ZF-DNA相互作用表现出形态灵活性,适应序列变化.
- 这些发现为哺乳动物发育和进化中ZF-DNA相互作用的进化和结构基础提供了关键的见解.
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