同时的蛋白质组定位和周转分析揭示了蛋白质平衡中断的时空特征
Jordan Currie1, Vyshnavi Manda1, Sean K Robinson1
1Department of Medicine, University of Colorado School of Medicine, Aurora, CO, 80045, USA.
Nature communications
|March 12, 2024
概括
这项研究引入了同时蛋白质定位和周转 (SPLAT) 来测量蛋白质的位置和周转. SPLAT揭示了细胞压力和药物如何影响蛋白质动态和平衡.
科学领域:
- 蛋白质组学是指蛋白质组学.
- 细胞生物学 细胞生物学
- 生物化学 生物化学
背景情况:
- 蛋白质的空间和时间动态对于功能至关重要,但很难测量.
- 现有的方法无法同时评估蛋白质周转和亚细胞局部化.
研究的目的:
- 开发一种基于质谱的蛋白质组学策略,即同时蛋白质位和周转 (SPLAT),用于同时测量蛋白质周转率和亚细胞局部化.
- 为了研究未折叠蛋白质响应 (UPR) 对人类AC16细胞中的蛋白质稳态的影响.
- 检查卡菲尔佐米布在诱导多能干细胞衍生心肌细胞 (iPSC-CM) 心脏毒性模型中对蛋白质平衡的作用.
主要方法:
- 同时蛋白质组定位和周转 (SPLAT) 使用质谱学.
- 在UPR条件下,SPLAT在人类AC16细胞中的应用.
- 在用卡菲尔佐米布治疗的iPSC-CM模型中应用SPLAT.
主要成果:
- UPR根据亚细胞位置对蛋白质周转有不同的影响,ER和戈尔吉压力蛋白质的全球减速但加速.
- UPR诱导广泛的差异性蛋白质定位,影响RNA结合蛋白和氨基酸载体.
- 像EGFR这样的新合成的蛋白质在压力下显示出改变的局部化,这表明贩运中断.
- 矛盾的是,carfilzomib对全球蛋白质半衰期的影响很小,但在iPSC-CM中选择性地破坏了sarcomere蛋白质平衡.
结论:
- SPLAT提供了关于蛋白质空间和时间动态之间的相互作用的见解.
- 该方法可以检查细胞应激和药物反应期间的蛋白质稳态调节.
- 细胞应激和药物治疗可以导致蛋白质周转和局部化的复杂,取决于位置的变化.
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