对FIR RRM1-FUSE相互作用的监管机制的结构洞察
Xiaomin Ni1,2, Andreas C Joerger1,2, Apirat Chaikuad1,2
1Institute of Pharmaceutical Chemistry, Goethe-University Frankfurt, Max-von-Laue-Str. 9, 60438 Frankfurt, Germany.
Open biology
|May 30, 2023
概括
FUBP相互作用抑制剂 (FIR) 蛋白质结构揭示了它如何与MYC基因促进体结合. 这种相互作用对于调节MYC转录至关重要,影响原型瘤基因活性.
科学领域:
- 分子生物学分子生物学
- 结构生物学 结构生物学
- 遗传学 是一个遗传学.
背景情况:
- 与FUBP相互作用的抑制剂 (FIR) 抑制原瘤基因MYC.的转录.
- 在MYC促进器中,FIR与远上游元素 (FUSE) 结合.
- FIR和FUSE结合蛋白1 (FUBP1) 之间的竞争是MYC转录调节的关键.
研究的目的:
- 阐明FIR与FUSE DNA相互作用的结构机制.
- 了解FIR的RRM域如何识别特定的DNA序列.
主要方法:
- 确定了FIR RRM1-2域与单链FUSEDNA结合的晶体结构.
- 与其他RRM-DNA/RNA复合体进行了比较结构分析.
- 进行局部定向突变发生 (Y115F替代) 以评估结合亲缘关系.
主要成果:
- 揭示了FIR RRM域与FUSE DNA的独特结合模式和分子间相互作用.
- 确定FIR为Y型RRM,类似于其他RRM,在保留的RNP2动图位置上含有氨酸.
- 证明Y115F替代物显著改变FIR的DNA结合亲和力.
结论:
- 提供了第一个对FIR的DNA结合机制的结构性见解.
- 突出了保存的芳香残留物 (位于115位的氨酸) 在FIR-ssDNA相互作用中的关键作用.
- 建立了进一步对FIR和MYC监管进行机制研究的结构基础.
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