表面电荷可以调节多域蛋白的相分离
Jonggul Kim1,2, Sanbo Qin3, Huan-Xiang Zhou3,4
1Department of Biophysics, University of Texas Southwestern Medical Center, Dallas, Texas 75390, United States.
Journal of the American Chemical Society
|January 23, 2024
概括
像SUMO这样的蛋白质的表面电荷可以控制生物分子凝聚物的形成. 修改胺残留物会改变相位分离,提供治疗和进化见解.
科学领域:
- 生物化学
- 分子生物学
- 生物物理
背景情况:
- 生物分子凝聚物通过相分离形成,由多价值蛋白相互作用驱动.
- 影响相分离的折叠域的物理性质尚不清楚.
研究的目的:
- 使用模型系统调查域表面电荷如何影响多价值驱动的相分离.
- 探索胺质子化在调节相位分离中的作用.
主要方法:
- 采用了一个包含小泛素修饰剂 (SUMO) 和SUMO相互作用动机 (SIM) 的模型系统.
- 操纵pH以改变histidine质子化状态,并观察到对polySUMO和polySIM相位分离的影响.
- 使用胺突变来评估它们对蛋白质溶解度和相分离的影响.
- 使用原子模型量化解释观察到的弱相互作用.
主要成果:
- polySUMO和polySIM的相分离对pH值变化敏感,与SUMO表面的histidine质子化有关.
- 基因突变模仿了pH效应,同时改变了SUMO的溶解度和相位分离.
- 原子模型成功地解释了控制相分离的弱相互作用.
结论:
- 表面电荷是调整多价蛋白的相分离的关键因素.
- 这一发现表明了生物控制,进化适应和相隔过程中的治疗干预机制.
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