通过核孔确定蛋白质的表面特性
Steffen Frey1, Renate Rees1, Jürgen Schünemann1
1Department of Cellular Logistics, Max Planck Institute for Biophysical Chemistry, Göttingen, Germany.
Cell
|June 30, 2018
概括
分子的表面特性极大地影响它们通过核孔综合体 (NPC) 的运输速度. 重新设计的蛋白质显示出极大变化的通道速度,甚至影响受体介导的核传输.
科学领域:
- 分子生物学
- 细胞生物学
- 生物物理
背景情况:
- 核孔复合体 (NPC) 通过选择性屏障调节细胞核和细胞质之间的运输.
- 在NPC中的FG域屏障控制分子的通过.
研究的目的:
- 研究移动物种的表面特征如何通过NPC影响它们的转移率.
- 了解控制分子通道的原理,并将其应用于工程运输速率.
主要方法:
- 对充电,极性和疏水残留物对NPC通道的影响的分析.
- 计算机建模以探索潜在的相互作用,例如-π相互作用.
- 有修改表面特性的绿色光蛋白 (GFP) 变体的工程.
- 改变运输特征的工程GFP变体的结构分析.
主要成果:
- 负电荷和素阻碍NPC通过,而疏水残留物,某些极性残留物 (Cys,His) 和素则促进它.
- 工程 GFP 变种表现出广泛的传输速度,从 35 倍慢到大约 500 倍快.
- 最快的GFP变种超过了自然核传输受体 (NTR) 的传输速度.
- 结构洞察力揭示了工程受体如何有效地结合FG图案.
- 货物表面特性对转移率有很大影响,即使是在NTR中介运输中.
结论:
- 分子表面特性是NPC通道速率的关键决定因素.
- 理性设计可以通过NPC大大改变蛋白质运输动力学,超过自然运输效率.
- 货物特性在核运输的效率上起着至关重要的作用,包括受体介导途径.
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