用光亲和基蛋白质识别多ADP-ribose结合蛋白质
Morgan Dasovich1,2, Morgan Q Beckett3, Scott Bailey2,3
1Department of Chemistry, Krieger School of Arts and Sciences, Johns Hopkins University, Baltimore, Maryland 21218, United States.
Journal of the American Chemical Society
|February 17, 2021
概括
研究人员发现了与DNA损伤反应中的关键分子 - - 聚甲酸 (PAR) 结合的蛋白质. 这项研究揭示了参与RNA处理和代谢的新型PAR结合蛋白,进步了对癌症治疗的理解.
科学领域:
- 生物化学
- 分子生物学
- 蛋白质组学
背景情况:
- 聚ADP- 核糖 (PAR) 对于DNA损伤反应至关重要,并且是癌症治疗的目标.
- PAR的分子功能和结合伙伴仍然不完全理解.
- 识别PAR结合蛋白对于阐明PAR信号通路至关重要.
研究的目的:
- 开发一种用于识别内源性多基糖 (PAR) 结合蛋白的方法.
- 创建包括新候选物在内的PAR结合蛋白的全面普查.
- 研究PAR聚合物长度在蛋白质结合和信号传递中的作用.
主要方法:
- 一个新的PAR相亲探测器的合成.
- 捕获和分离内源性PAR结合蛋白.
- 使用拉下和电泳移动性转移试验确认PAR结合.
- 使用定义长度的 PAR 探针对蛋白质结合的选择性进行分析.
主要成果:
- 鉴定了几十种已知和数百种新的PAR结合蛋白.
- 证实了八种新型候选蛋白的PAR结合.
- 证明了长度依赖的PAR结合,蛋白质更喜欢更长的PAR链 (40-mer而不是8-mer).
- 与RNA代谢和生物分子凝聚物形成的PAR结合.
结论:
- 这项研究提供了PAR结合蛋白的首次全面统计.
- PAR聚合物长度是PAR蛋白相互作用和信号的关键调节器.
- 新发现的PAR结合蛋白在癌症和其他疾病中具有潜在的治疗点.
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