在 arginyltransferase 1 (ATE1) 中识别一个内在无序区域 (IDR)
Misti Cartwright1, Rinky Parakra2, Ayomide Oduwole1
1Department of Chemistry and Biochemistry, University of Maryland, Baltimore County, Baltimore, Maryland, 21250 USA.
bioRxiv : the preprint server for biology
|September 4, 2024
概括
鼠 Arginyltransferase 1 (ATE1) 具有复杂的结构,与酵母ATE1不同,具有内在无序区域 (IDR). 这种IDR可能有助于化复合体的形成,为哺乳动物ATE1功能提供了新的见解.
科学领域:
- 生物化学 生物化学
- 结构生物学 结构生物学
- 分子生物学分子生物学
背景情况:
- 甲基转移酶1 (ATE1) 对于甲基化至关重要,这是一个对细胞平衡至关重要的翻译后修饰.
- ATE1功能障碍与神经退行性和心血管疾病以及病毒活性 (例如,SARS-CoV-2,HIV) 有关.
- 之前的研究集中在酵母ATE1上,哺乳动物ATE1机制尚不清楚.
研究的目的:
- 在结构和生物物理上描述老鼠 (Mus musculus) ATE1.1.
- 阐明哺乳动物和酵母之间的结构差异ATE1.1.
- 调查ATE1结构特征的功能影响.
主要方法:
- 尺寸排除色谱 (SEC) 是一种尺寸排除色谱.
- 微角X射线散射 (SAXS) 是一种微角X射线散射技术.
- 二交换质谱法 (HDX-MS) 是一种方法.
- 在AlphaFold建模中使用AlphaFold模型.
- 生物信息学分析
主要成果:
- 与酵母ATE1.1相比,老鼠ATE1的结构复杂性更大.
- 所有研究的小鼠ATE1拼接变体都具有内在无序区域 (IDR).
- 酵母ATE1缺乏可比的IDR,通过比较HDX-MS证实了这一点.
- 生物信息学在哺乳动物和其他真核生物ATE1.1.中确定了IDR类序列.
结论:
- 哺乳动物ATE1具有独特的内在无序区域 (IDR),在酵母ATE1中不存在.
- IDR位于ATE1活性部位附近,可能会与tRNAArg.进行相互作用.
- 这一发现增加了ATE1结构和功能的复杂性,指导了未来的研究.
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