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FUS 阶段分离是通过分子伴奏和氨酸-π 相互作用的甲基化调节的
Seema Qamar1, GuoZhen Wang1, Suzanne J Randle1
1Cambridge Institute for Medical Research, Department of Clinical Neurosciences, University of Cambridge, Cambridge CB2 0XY, UK.
Cell
|April 21, 2018
概括
由氨酸低甲基化驱动的FUS蛋白质凝结导致前叶退化 (FTLD). 运输蛋白作为一个伴侣, 防止FUS凝结和拯救神经元功能.
科学领域:
- 生物化学
- 分子生物学
- 神经科学
背景情况:
- 蛋白质的可逆相分离,就像FUS一样,对于没有膜的有机体至关重要.
- FUS的内在无序的低复杂性 (LC) 域驱动了这种相位分离.
研究的目的:
- 调查-π相互作用和氨酸甲基化在FUS阶段分离中的作用.
- 了解FUS凝结如何导致前叶退化 (FTLD).
- 确定FUS阶段分离的生理调节剂及其治疗潜力.
主要方法:
- 对FUS低复杂性域和C端域的分析.
- 研究氨酸和氨酸残留物之间的氨酸-π相互作用.
- 评估翻译后阿基因甲基化对FUS相分离的影响.
- 研究运输素作为FUS分子护理者的作用.
主要成果:
- 涉及氨酸和氨酸的合作性-π相互作用有助于FUS阶段分离.
- 氨酸低甲基化显著促进FUS阶段分离和凝.
- 低甲基化FUS形成稳定,富含β片的水凝,破坏RNP颗粒的功能并损害蛋白质合成.
- 运输蛋白作为一个伴侣,减少FUS阶段分离和拯救蛋白质合成.
结论:
- FUS阶段分离是通过-π相互作用和氨酸甲基化进行调节的.
- 低甲基化诱导的FUS凝结是FTLD病变的一个关键机制.
- 运输素在预防病态FUS凝结和维持神经元功能方面发挥着至关重要的作用.
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