生物分子液体-液体相分离的调节通过偏好的水合和小奥斯莫利特与蛋白质的相互作用
Keiji Kitamura1, Ayano Oshima2, Fuka Sasaki1
1Graduate School of Pharmacy, Ritsumeikan University, 1-1-1 Nojihigashi, Kusatsu, Shiga 525-8577, Japan.
The journal of physical chemistry letters
|July 19, 2024
概括
三甲基胺N-氧化物 (TMAO) 稳定生物分子液体液相分离 (LLPS),而尿素则使其不稳定. 这些氧化物调节FUS蛋白LLPS通过偏好的水合和直接相互作用,即使在极端条件下.
科学领域:
- 生物物理学的生物物理.
- 生物化学 生物化学
- 蛋白质化学 蛋白质化学
背景情况:
- 液-液相分离 (LLPS) 对于细胞组织至关重要.
- 在瘤中融化 (FUS) 蛋白经历LLPS,形成无膜有机体.
- 已知像TMAO和尿素这样的奥斯莫利特会影响蛋白质的行为.
研究的目的:
- 研究TMAO和尿素对FUS蛋白LLPS的影响.
- 了解LLPS.由溶体诱导的调制背后的机制.
- 在各种条件下探索LLPS,包括高盐和高压.
主要方法:
- 在温度和压力扫描下测量度.
- 在大气和高压条件下分析FUS-LLPS状态.
- 将m值概念应用于解蛋白相互作用的应用.
主要成果:
- TMAO稳定了FUS LLPS,这是由于其排除的体积效应 (偏好的水合).
- 尿素破坏FUS LLPS的稳定性,这与其与蛋白质的优先相互作用有关.
- TMAO对抗尿素对LLPS的破坏性作用,这是一个新的观察.
结论:
- 生物分子LLPS可以通过解体相互作用,特别是偏好的水合和直接蛋白质相互作用来调整.
- 即使在具有挑战性的环境中 (高盐,尿素,压力) 也可以促进LLPS.
- 这些发现提供了关于在压力下细胞组织和蛋白质行为的见解.
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